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Probability of high-risk genetic matching with oocyte and semen donors: complete gene analysis or genotyping test?

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To estimate the probability of high-risk genetic matching when assisted reproductive techniques (ART) are applied with double gamete donation, following an NGS carrier test based on a complete study of the genes concerned. We then determine the results that would have been obtained if the genotyping tests most widely used in Spanish gamete banks had been applied.

Methods

In this descriptive observational study, 1818 gamete donors were characterised by NGS. The pathogenic variants detected were analysed to estimate the probability of high-risk genetic matching and to determine the results that would have been obtained if the three most commonly used genotyping tests in ART had been applied.

Results

The probability of high-risk genetic matching with gamete donation, screened by NGS and complete gene analysis, was 5.5%, versus the 0.6–2.7% that would have been obtained with the genotyping test. A total of 1741 variants were detected, including 607 different variants, of which only 22.6% would have been detected by all three genotyping tests considered and 44.7% of which would not have been detected by any of these tests.

Conclusion

Our study highlights the considerable heterogeneity of the genotyping tests, which present significant differences in their ability to detect pathogenic variants. The complete study of the genes by NGS considerably reduces reproductive risks when genetic matching is performed with gamete donors. Accordingly, we recommend that carrier screening in gamete donors be carried out using NGS and a complete study with nontargeted analysis of the variants of the screened genes.

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References

  1. Calhaz-Jorge C, De Geyter C, Kupka MS, De Mouzon J, Erb K, Mocanu E, et al. Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE. Hum Reprod. 2016;31:1638–52.

    Article  CAS  PubMed  Google Scholar 

  2. Gliozheni O, Hambartsoumian E, Strohmer H, Petrovskaya E, Tishkevich O, Bogaerts K, et al. ART in Europe, 2016: results generated from European registries by ESHRE†. Hum Reprod Open. 2020;2020:1–17.

    Google Scholar 

  3. Dondorp W, De Wert G, Pennings G, Shenfield F, Devroey P, Tarlatzis B, et al. ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues. Hum Reprod. 2014;29:1353–9.

    Article  CAS  PubMed  Google Scholar 

  4. Practice T, Medicine R, Technology R. Recommendations for gamete and embryo donation: a committee opinion. Fertil Steril. American Society for Reproductive Medicine. 2013;99:47–62.e1. Available from: https://doi.org/10.1016/j.fertnstert.2012.09.037

  5. Castilla JA, Abellán F, Alamá F, Aura M, Bassas Ll, Clúa E, de la Fuente A, Guillén JJ, Manau D, Rueda J, Ruiz M VX. Genetic screening in gamete donation: recommendations from SEF, ASESA, AEBM-ML, ASEBIR and AEGH. Med Reprod y Embriol Clin. 2020;7:1–4.

  6. Haque IS, Lazarin GA, Kang HP, Evans EA, Goldberg JD, Wapner RJ. Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA - J Am Med Assoc. 2016;316:734–42.

    Article  Google Scholar 

  7. Lazarin GA, Haque IS, Nazareth S, Iori K, Patterson AS, Jacobson JL, et al. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Genet Med. 2013;15:178–86.

    Article  PubMed  Google Scholar 

  8. Arjunan A, Litwack K, Collins N, Charrow J. Carrier screening in the era of expanding genetic technology. Genet Med. 2016;18:1214–7.

    Article  CAS  PubMed  Google Scholar 

  9. Azimi M, Schmaus K, Greger V, Neitzel D, Rochelle R, Dinh T. Carrier screening by next-generation sequencing: health benefits and cost effectiveness. Mol Genet Genomic Med. 2016;4:292–302.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nazareth SB, Lazarin GA, Goldberg JD. Changing trends in carrier screening for genetic disease in the United States. Prenat Diagn. 2015;35:931–5.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Prior TW. Next-generation carrier screening: are we ready? Genome Med. 2014;6:1–3.

    Article  Google Scholar 

  12. Sims CA, Callum P, Ray M, Iger J, Falk RE. Genetic testing of sperm donors: survey of current practices. Fertil Steril. 2010;94:126–9. Available from: https://doi.org/10.1016/j.fertnstert.2009.01.139

  13. Abulí A, Boada M, Rodríguez-Santiago B, Coroleu B, Veiga A, Armengol L, et al. NGS-based assay for the identification of individuals carrying recessive genetic mutations in reproductive medicine. Hum Mutat. 2016;37:516–23.

    Article  PubMed  Google Scholar 

  14. Martin J, Asan, Yi Y, Alberola T, Rodríguez-Iglesias B, Jiménez-Almazán J, et al. Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology. Fertil Steril. 2015;104:1286–93.

  15. Punj S, Akkari Y, Huang J, Yang F, Creason A, Pak C, et al. Preconception carrier screening by genome sequencing: results from the clinical laboratory. Am J Hum Genet [Internet]. ElsevierCompany. 2018;102:1078–89. Available from: https://doi.org/10.1016/j.ajhg.2018.04.004

  16. World Health Organization. WHO laboratory manual for the examination and processing of human semen. Fifth Ed. 2010. p. http://whqlibdoc.who.int/publications/2010/9789241.

  17. Ciotti P, Di Maria E, Bellone E, Ajmar F, Mandich P. Triplet repeat primed PCR (TP PCR) in molecular diagnostic testing for Friedreich ataxia. J Mol Diagnostics. 2004;6:285–9.

    Article  CAS  Google Scholar 

  18. Campuzano V, Montermini L, Moltò M. D., Pianese L, Cossée M, Cavalcanti F,Monros E, Rodius F, Duclos F, Monticelli A, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic gaa triplet repeat expansion. Science (New York, N.Y.) 1996;271:1423–7.

  19. Xunclà M, Rodríguez-Revenga L, Madrigal I, Jiménez D, Milà M, Badenas C. Protocol proposal for Friedreich ataxia molecular diagnosis using fluorescent and triplet repeat primed polymerase chain reaction., J Lab Clin Med. 2010;156:309–14.

  20. Chen L, Hadd A, Sah S, Filipovic-Sadic S, Krosting J, Sekinger E, et al. An information-rich CGG repeat primed PCR that detects the full range of fragile X expanded alleles and minimizes the need for southern blot analysis. J Mol Diagnostics [Internet]. American Society for Investigative Pathology and Association for Molecular Pathology; 2010;12:589–600. Available from: https://doi.org/10.2353/jmoldx.2010.090227

  21. Rossetti LC, Radic CP, Larripa IB, De Brasi CD. Developing a new generation of tests for genotyping hemophilia-causative rearrangements involving int22h and int1h hotspots in the factor VIII gene. J Thromb Haemost. 2008;6:830–6.

    Article  CAS  PubMed  Google Scholar 

  22. Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagnostics [Internet]. American Society for Investigative Pathology and the Association for Molecular Pathology. 2017;19:4–23. Available from: https://doi.org/10.1016/j.jmoldx.2016.10.002

  23. Ceyhan-Birsoy O, Ceyhan-Birsoy O, Murry JB, Machini K, Lebo MS, Rehm HL, et al. Interpretation of genomic sequencing results in healthy and ill newborns: results from the BabySeq Project. Am J Hum Genet. 2019;104:76–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Molina M, Yoldi A, Navas P, Gañán M, Vaquero Á, del Pico JL, et al. Carriers of cystic fibrosis among sperm donors: complete CFTR gene analysis versus CFTR genotyping. Fertil Steril. 2020;114:524–34.

    Article  CAS  PubMed  Google Scholar 

  25. Silver AJ, Larson JL, Silver MJ, Lim RM, Borroto C, Spurrier B, et al. Carrier screening is a deficient strategy for determining sperm donor eligibility and reducing risk of disease in recipient children. Genet Test Mol Biomarkers. 2016;20:276–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yang S, Lincoln SE, Kobayashi Y, Nykamp K, Nussbaum RL, Topper S. Sources of discordance among germ-line variant classifications in ClinVar. Genet Med. Nature Publishing Group. 2017;19:1118–26. Available from: https://doi.org/10.1038/gim.2017.60

  27. Amendola LM, Jarvik GP, Leo MC, McLaughlin HM, Akkari Y, Amaral MD, et al. Performance of ACMG-AMP variant-interpretation guidelines among nine laboratories in the clinical sequencing exploratory research consortium. Am J Hum Genet. American Society of Human Genetics. 2016;98:1067–76. Available from: https://doi.org/10.1016/j.ajhg.2016.03.024

  28. Ben-Shachar R, Svenson A, Goldberg JD, Muzzey D. A data-driven evaluation of the size and content of expanded carrier screening panels. Genet Med [Internet]. Springer US; 2019;21:1931–9. Available from: https://doi.org/10.1038/s41436-019-0466-5

  29. Chokoshvili D, Vears DBP. Expanded carrier screening for monogenic disorders: where are we now? Prenat Diagn. 2018;38:59–66.

    Article  PubMed  Google Scholar 

  30. Henneman L, Borry P, Chokoshvili D, Cornel MC, Van El CG, Forzano F, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet. 2016;24:e1-12.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tonin R, Caciotti A, Funghini S, Pasquini E, Mooney SD, Cai B, et al. Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation. BBA Clin. 2016;5:114–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hoffmann L, Haussmann U, Mueller M, Spiekerkoetter U. VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment. J Inherit Metab Dis. 2012;35:269–77.

    Article  CAS  PubMed  Google Scholar 

  33. Pena LDM, Calcar SCV, Hansen J, Edick MJ, Walsh C, Leslie N, et al. Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database. Molec Genet Metab. 2017;118:272–81.

    Article  Google Scholar 

  34. Evans M, Andresen BS, Nation J, Boneh A. VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria. Mol Genet Metab. 2016;118:282–7.

    Article  CAS  PubMed  Google Scholar 

  35. Santamaria R, Esposito G, Vitagliano L, Race V, Paglionico I, Zancan L, et al. Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase. Biochem J. 2000;350:823–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Balmer C, Pandey AV, Rüfenacht V, Nuoffer JM, Fang P, Wong LJ, et al. Mutations and polymorphisms in the human argininosuccinate lyase (ASL) gene. Hum Mutat. 2014;35:27–35.

    Article  CAS  PubMed  Google Scholar 

  37. Carranza D, Vega AK, Torres-Rusillo S, Montero E, Martinez LJ, Santamaría M, et al. Molecular and functional characterization of a cohort of Spanish patients with ataxia-telangiectasia. NeuroMolecular Med. 2017;19:161–74.

    Article  CAS  PubMed  Google Scholar 

  38. Carney EF, Srinivasan V, Moss PA, Taylor AM. Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95. J Immunol. 2012;189:261–8.

    Article  CAS  PubMed  Google Scholar 

  39. Margarit E, Bach V, Gómez D, Bruguera M, Jara P, Queralt R, et al. Mutation analysis of Wilson disease in the Spanish population—identification of a prevalent substitution and eight novel mutations in the ATP7B gene. Clin Genet. 2005;68:61–8.

    Article  CAS  PubMed  Google Scholar 

  40. Cox DW, Prat L, Walshe JM, Heathcote J, Gaffney D. Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry. Hum Mutat. 2005;26:280.

    Article  CAS  PubMed  Google Scholar 

  41. Davies LP, Macintyre G, Cox DW. New mutations in the Wilson disease gene, ATP7B: implications for molecular testing. Genet Test. 2008;12:139–45.

    Article  CAS  PubMed  Google Scholar 

  42. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, et al. A genetic study of Wilson’s disease in the United Kingdom. Brain. 2013;136:1476–87.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Vrabelova S, Letocha O, Borsky M, Kozak L. Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab. 2005;86:277–85.

    Article  CAS  PubMed  Google Scholar 

  44. Simsek Papur O, Akman SA, Cakmur R, Terzioglu O. Mutation analysis of ATP7B gene in Turkish Wilson disease patients: identification of five novel mutations. Eur J Med Genet. 2013;56:175–9.

    Article  PubMed  Google Scholar 

  45. Papur OS, Terzioglu O, Koc A. Functional characterization of new mutations in Wilson disease gene (ATP7B) using the yeast model. J Trace Elem Med Biol. 2015;31:33–6.

    Article  CAS  PubMed  Google Scholar 

  46. Fanin M, Nascimbeni AC, Tasca E, Angelini C. How to tackle the diagnosis of limb-girdle muscular dystrophy 2A. Eur J Hum Genet. 2009;17:598–603.

    Article  CAS  PubMed  Google Scholar 

  47. Sevy A, Cerino M, Gorokhova S, Dionnet E, Mathieu Y, Verschueren A, et al. Improving molecular diagnosis of distal myopathies by targeted next-generation sequencing. J Neurol Neurosurg Psychiatry. 2016;87:340–2.

    Article  PubMed  Google Scholar 

  48. Piluso G, Politano L, Aurino S, Fanin M, Ricci E, Ventriglia VM, et al. Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes. J Med Genet. 2005;42:686–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jaka O, Azpitarte M, Paisán-Ruiz C, Zulaika M, Casas-Fraile L, Sanz R, et al. Entire CAPN3 gene deletion in a patient with limb-girdle muscular dystrophy type 2A. Muscle Nerve. 2014;50:448–53.

    Article  CAS  PubMed  Google Scholar 

  50. Sebastio G, De FR, Andria G, Kluijtmans LAJ, Blom H, Boers GHJ, et al. Cystathionine β-synthase mutations in homocystinuria. Hum Mutat. 1999;13:362–75.

    Article  PubMed  Google Scholar 

  51. Janošík M, Sokolová J, Janošíková B, Krijt J, Klatovská V, Kožich V. Birth prevalence of homocystinuria in Central Europe: frequency and pathogenicity of mutation c.1105C>T (p.R369C) in the cystathionine beta-synthase gene. J Pediatr. 2009;154:431–7.

  52. Sommen M, Schrauwen I, Vandeweyer G, Boeckx N, Corneveaux JJ, van den Ende J, et al. DNA diagnostics of hereditary hearing loss: a targeted resequencing approach combined with a mutation classification system. Hum Mutat. 2016;37:812–9.

    Article  CAS  PubMed  Google Scholar 

  53. Aparisi MJ, Aller E, Fuster-García C, García-García G, Rodrigo R, Vázquez-Manrique RP, et al. Targeted next generation sequencing for molecular diagnosis of Usher syndrome. Orphanet J Rare Dis. 2014;9.

  54. Moteki H, Azaiez H, Booth K, Shearer AE, Sloan CM, Kolbe DL, et al. Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population. Clin Genet. 2017;89:466–72.

    Article  Google Scholar 

  55. Besnard T, García-García G, Baux D, Vaché C, Faugére V, Larrieu L, et al. Experience of targeted Usher exome sequencing as a clinical test. Mol Genet Genomic Med. 2014;2:30–43.

    Article  PubMed  Google Scholar 

  56. Astuto LM, Bork JM, Weston MD, Askew JW, Fields RR, Orten DJ, et al. CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness. Am J Hum Genet. 2002;71:262–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zaneveld J, Siddiqui S, Li H, Wang X, Wang H, Wang K, et al. Comprehensive analysis of patients with Stargardt macular dystrophy reveals new genotype-phenotype correlations and unexpected diagnostic revisions. Genet Med. 2015;17:262–70.

    Article  CAS  PubMed  Google Scholar 

  58. Jaijo T, Aller E, García-García G, Aparisi MJ, Berna S, Ávila-Fernández A, et al. Microarray-based mutation analysis of 183 Spanish families with Usher syndrome. Investig Ophthalmol Vis Sci. 2010;51:1311–7.

    Article  Google Scholar 

  59. Ganapathy A, Pandey N, Srisailapathy CRS, Jalvi R, Malhotra V, Venkatappa M, et al. Non-syndromic hearing impairment in India: high allelic heterogeneity among mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE. PLoS One. 2014;9.

  60. Grody WW, Cutting GR, Klinger KW, Richards CS, Watson MS, Desnick RJ. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med. 2001;3:149–54.

    Article  CAS  PubMed  Google Scholar 

  61. Casals T, De-Gracia J, Gallego M, Dorca J, Rodríguez-Sanchón B, Ramos MD, et al. Bronchiectasis in adult patients: an expression of heterozygosity for CFTR gene mutations? Clin Genet. 2004;65:490–5.

    Article  CAS  PubMed  Google Scholar 

  62. Tzetis M, Efthymiadou A, Strofalis S, Psychou P, Dimakou A, Pouliou E, et al. CFTR gene mutations—including three novel nucleotide substitutions—and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease. Hum Genet. 2001;108:216–21.

    Article  CAS  PubMed  Google Scholar 

  63. Martinez B, Heller M, Gaitch N, Hubert D, Burgel PR, Levy P et al. p.Arg75Gln, a CFTR variant involved in the risk of CFTR-related disorders? J Hum Genet. 2014;59:206–10.

  64. Divac A, Nikolic A, Mitic-Milikic M, Nagorni-Obradovic L, Petrovic-Stanojevic N, Dopudja-Pantic V, et al. High frequency of the R75Q CFTR variation in patients with chronic obstructive pulmonary disease. J Cyst Fibros. 2004;3:189–91.

    Article  CAS  PubMed  Google Scholar 

  65. Borowitz D. CFTR, bicarbonate, and the pathophysiology of cystic fibrosis. Pediatr Pulmonol. 2015;50:S24–30.

    Article  PubMed  Google Scholar 

  66. Strom CM, Redman JB, Peng M. The dangers of including nonclassical cystic fibrosis variants in population-based screening panels: p.L997F, further genotype/phenotype correlation data. Genet Med. 2011;13:1042–1044.

  67. Hamoir C, Pepermans X, Piessevaux H, Jouret-Mourin A, Weynand B, Habyalimana JB, et al. Clinical and morphological characteristics of sporadic genetically determined pancreatitis as compared to idiopathic pancreatitis: higher risk of pancreatic cancer in CFTR variants. Digestion. 2013;87:229–39.

    Article  CAS  PubMed  Google Scholar 

  68. Gomez M, Benetazzo MG, Marzari MG, Bombieri C, Belpinati F, Castellani C, et al. High frequency of cystic fibrosis transmembrane regulator mutation L997F in patients with recurrent idiopathic pancreatitis and in newborns with hypertrypsinemia. Am J Hum Genet. 2000;66:2013–4.

    Article  Google Scholar 

  69. Keiles S, Kammesheidt A. Identification of CFTR, PRSS1 and SPINK1 mutations in 381 patients with pancreatitis. Pancreas. 2006;33:221–7.

    Article  CAS  PubMed  Google Scholar 

  70. Bergougnoux A, Viart V, Miro J, Bommart S, Molinari N, des Georges M et al. Should diffuse bronchiectasis still be considered a CFTR-related disorder? J Cyst Fibros. 2015;14:646–53.

  71. Grangeia A, Sá R, Carvalho F, Martin J, Girodon E, Silva J, et al. Molecular characterization of the cystic fibrosis transmembrane conductance regulator gene in congenital absence of the vas deferens. Genet Med. 2007;9:163–72.

    Article  CAS  PubMed  Google Scholar 

  72. Dal’Maso VB, Mallmann L, Siebert M, Simon L, Saraiva-Pereira ML, Dalcin Pde T. Diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator gene in patients suspected of having mild or atypical cystic fibrosis. J Bras Pneumol. 2013;39:181–9.

  73. Alonso MJ, Heine-Suñer D, Calvo M, Rosell J, Giménez J, Ramos MD, et al. Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry. Ann Hum Genet. 2007;71:194–201.

    Article  CAS  PubMed  Google Scholar 

  74. Casals T, Bassas L, Egozcue S, Ramos MD, Giménez J, Segura A, et al. Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens. Hum Reprod. 2000;15:1476–83.

    Article  CAS  PubMed  Google Scholar 

  75. Schrijver I, Ramalingam S, Sankaran R, Swanson S, Dunlop CL, Keiles S, et al. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. J Mol Diagn. 2005;7:289–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pelletier AL, Bienvenu T, Rebours V, O’Toole D, Hentic O, Maire F, et al. CFTR gene mutation in patients with apparently idiopathic pancreatitis: lack of phenotype-genotype correlation. Pancreatology. 2010;10:158–64.

    Article  CAS  PubMed  Google Scholar 

  77. Dörk T, Dworniczak B, Aulehla-Scholz C, Wieczorek D, Böhm I, Mayerova A, et al. Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens. Hum Genet. 1997;100:365–77.

    Article  PubMed  Google Scholar 

  78. De Wachter E, Thomas M, Wanyama SS, Seneca S, Malfroot A. What can the CF registry tell us about rare CFTR-mutations? A Belgian study. Orphanet J Rare Dis. 2017;12:142.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Masvidal L, Giménez J, Ramos MD, Domingo C, Farré A, Bassas L et al. The p.Arg258Gly mutation in intracellular loop 2 of CFTR is associated with CFTR-related disorders. Genet Test Mol Biomarkers. 2009;13:765–8.

  80. LaRusch J, Jung J, General IJ, Lewis MD, Woo Park H, Brand RE et al. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. PLoS Genet. 2014;10:e1004376

  81. Van Goor F, Yu H, Burton B, Hoffman BJ. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014;13:29–36.

    Article  PubMed  Google Scholar 

  82. Puéchal X, Bienvenu T, Génin E, Berthelot JM, Sibilia J, Gaudin P, et al. Mutations of the cystic fibrosis gene in patients with bronchiectasis associated with rheumatoid arthritis. Ann Rheum Dis. 2011;70:653–9.

    Article  PubMed  Google Scholar 

  83. Bernardino AL, Ferri A, Passos-Bueno MR, Kim CE, Nakaie CM, Gomes CE, et al. Molecular analysis in Brazilian cystic fibrosis patients reveals five novel mutations. Genet Test. 2000;4:69–74.

    Article  CAS  PubMed  Google Scholar 

  84. Boudaya M, Fredj SH, Haj RB, Khrouf M, Bouker A, Halouani L, et al. Cystic fibrosis transmembrane conductance regulator mutations and polymorphisms associated with congenital bilateral absence of vas deferens in a restricted group of patients from North Africa. Ann Hum Biol. 2012;39:76–9.

    Article  CAS  PubMed  Google Scholar 

  85. Giusti R, Badgwell A, Iglesias AD. New York State cystic fibrosis consortium: the first 2.5 years of experience with cystic fibrosis newborn screening in an ethnically diverse population. Pediatrics. 2007;119:e460–7.

  86. Bienvenu T, Hubert D, Setbon E, Dusser D, Kaplan J.C and Beldjord C. A novel missense mutation in exon 16 of the cystic fibrosis transmembrane conductance regulator (cftr) gene identified in cbavd patients. Hum Mutat. 1996;7:182.

  87. Dayangac D, Erdem H, Yilmaz E, Sahin A, Sohn C, Özgüc M, et al. Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens. Hum Reprod. 2004;19:1094–100.

    Article  CAS  PubMed  Google Scholar 

  88. Casals T, Bassas L, Egozcue S, Ramos MD, Giménez J, Segura A, et al. Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens. Hum Reprod. 2000;15:1476–83.

    Article  CAS  PubMed  Google Scholar 

  89. Havasi V, Keiles S, Hambuch T, Sorscher E.J, MD and Kammesheidt A. The role of the F508C mutation in congenital bilateral absence of the vas deferens. Genet in Medic.2008;10:12.

  90. Xiao Y, Yuan W, Yu Y, Yu B, Guo Y, Xu X, et al. Targeted gene next-generation sequencing in Chinese children with chronic pancreatitis and acute recurrent pancreatitis. J Pediatr. 2017;191:158–63.

    Article  CAS  PubMed  Google Scholar 

  91. Masson E, Chen JM, Audrézet MP, Cooper DN, Férec C. A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. PLoS One. 2013;8:e73522.

  92. Arduino C, Ferrone M, Brusco A, Garnerone S, Fontana D, Rolle L, et al. Congenital bilateral absence of vas deferens with a new missense mutation (P499A) in the CFTR gene. Clin Genet. 1988;53:202–4.

    Article  Google Scholar 

  93. Hasenpusch-Theil K, Bataille V, Laehdetie J, Obermayr F, Sampson J.R, Frischauf A.M. Gorlin syndrome: identification of 4 novel germ-line mutations of the human patched (PTCH) gene. Hum Mutat. 1997;11:480.

  94. Steiner B, Rosendahl J, Witt H, Teich N, Keim V, Schulz H-U, et al. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Hum Mutat. 2011;32:912–20.

    Article  CAS  PubMed  Google Scholar 

  95. Ratbi I, Legendre M, Niel F, Martin J, Soufir JC, Izard V, et al. Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Hum Reprod. 2007;22:1285–91.

    Article  CAS  PubMed  Google Scholar 

  96. de Prada A, Bütschi FN, Bouchardy I, Beckmann JS, Morris MA, Hafen GM, Fellmann F. [R74W;R1070W;D1270N]: a new complex allele responsible for cystic fibrosis. J Cyst Fibros. 2010;9:447–9.

    Article  Google Scholar 

  97. de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, et al. Genotype-phenotype correlation for pulmonary function in cystic fibrosis. Thorax. 2005;60:558–63.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Kilinç MO, Ninis VN, Dağli E, Demirkol M, Ozkinay F, Arikan Z, et al. Highest heterogeneity for cystic fibrosis: 36 mutations account for 75% of all CF chromosomes in Turkish patients. Am J Med Genet. 2002;113:250–7.

    Article  PubMed  Google Scholar 

  99. Kahnoski K, Khoo SK, Nassif NT, Chen J, Lobo GP, Segelov E, et al. Alterations of the Birt-Hogg-Dubé gene (BHD) in sporadic colorectal tumours. J Med Genet. 2003;40:511–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gomez M, Patuzzo C, Castellani C, Bovo P, Cavallini G, Mastella G, et al. CFTR and cationic trypsinogen mutations in idiopathic pancreatitis and neonatal hypertrypsinemia. Pancreatology. 2001;1:538–42.

    Article  Google Scholar 

  101. Nakano E, Masamune A, Niihori T, Kume K, Hamada S, Aoki Y, et al. Targeted next-generation sequencing effectively analyzed the cystic fibrosis transmembrane conductance regulator gene in pancreatitis. Dig Dis Sci. 2015;60:1297–307.

    Article  CAS  PubMed  Google Scholar 

  102. Jurkuvenaite A, Varga K, Nowotarski K, Kirk KL, Sorscher EJ, Li Y, et al. Mutations in the amino terminus of the cystic fibrosis transmembrane conductance regulator enhance endocytosis. J Biol Chem. 2006;281:3329–34.

    Article  CAS  PubMed  Google Scholar 

  103. Claustres M, Guittard C, Bozon D, Chevalier F, Verlingue C, Ferec C, et al. Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France. Hum Mutat. 2000;16:143–56.

    Article  CAS  PubMed  Google Scholar 

  104. Audrézet MP, Novelli G, Mercier B, Sangiuolo F, Maceratesi P, Férec C, et al. Identification of three novel cystic fibrosis mutations in a sample of Italian cystic fibrosis patients. Hum Hered. 1993;43:295–300.

    Article  PubMed  Google Scholar 

  105. Scotet V, De Braekeleer M, Audrézet MP, Lodé L, Verlingue C, Quéré I, et al. Prevalence of CFTR mutations in hypertrypsinaemia detected through neonatal screening for cystic fibrosis. Clin Genet. 2001;59:42–7.

    Article  CAS  PubMed  Google Scholar 

  106. Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, et al. Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis. Gastroenterology. 2011;140:162–71.

    Article  CAS  PubMed  Google Scholar 

  107. Mak V, Zielenski J, Tsui LC, Durie P, Zini A, Martin S, et al. Proportion of cystic fibrosis gene mutations not detected by routine testing in men with obstructive azoospermia. JAMA. 1999;281:2217–24.

    Article  CAS  PubMed  Google Scholar 

  108. Padoan R, Genoni S, Moretti E, Seia M, Giunta A, Corbetta C. Genetic and clinical features of false-negative infants in a neonatal screening programme for cystic fibrosis. Acta Paediatr. 2002;91:82–7.

    Article  CAS  PubMed  Google Scholar 

  109. Escámez MJ, García M, Cuadrado-Corrales N, Llames SG, Charlesworth A, De Luca N, et al. The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: C.6527insC disclosed as an unusually recurrent mutation. Br J Dermatol. 2010;163:155–61.

  110. Hovnanian A, Rochat A, Bodemer C, Petit E, Rivers CA, Prost C, et al. Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation. Am J Hum Genet. 1997;61:599–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Varki R, Sadowski S, Uitto J, Pfendner E. Epidermolysis bullosa. II. Type VII collagen mutations and pnenotype-genotype correlations in the dystrophic subtypes. J Med Genet. 2007;44:181–92.

  112. Almaani N, Liu L, Dopping-Hepenstal PJC, Lai-Cheong JE, Wong A, Nanda A, et al. Identical glycine substitution mutations in type VII collagen may underlie both dominant and recessive forms of dystrophic epidermolysis bullosa. Acta Derm Venereol. 2011;91:262–6.

    Article  PubMed  Google Scholar 

  113. Mahto A, McGrath JA, Deroide F, Rustin MHA. Late-onset pretibial recessive dystrophic epidermolysis bullosa. Clin Exp Dermatol. 2013;38:630–2.

    Article  CAS  PubMed  Google Scholar 

  114. Winberg JO, Hammami-Hauasli N, Nilssen Ø, Anton-Lamprecht I, Naylor SL, Kerbacher K, et al. Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene. Hum Mol Genet. 1997;6:1125–35.

    Article  CAS  PubMed  Google Scholar 

  115. Christiano A.M, McGrath J.A and Uitto J. Influence of the second COL7A1 mutation in determining the phenotypic severity of recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 1996; 106:766–770.

  116. Saeidian AH, Youssefian L, Moreno Trevino MG, Fortuna G, Vahidnezhad H, Atanasova VS, et al. Seven novel COL7A1 mutations identified in patients with recessive dystrophic epidermolysis bullosa from Mexico. Clin Exp Dermatol. 2018;43:579–84.

    Article  CAS  PubMed  Google Scholar 

  117. Gardella R, Zoppi N, Ferraboli S, Marini D, Tadini G, Barlati S, et al. Three homozygous PTC mutations in the collagen type VII gene of patients affected by recessive dystrophic epidermolysis bullosa: analysis of transcript levels in dermal fibroblasts. Hum Mutat. 1999;13:439–52.

    Article  CAS  PubMed  Google Scholar 

  118. Fassihi H, Renwick PJ, Black C, McGrath JA. Single cell pcr amplification of microsatellites flanking the COL7A1 gene and suitability for preimplantation genetic diagnosis of hallopeau-siemens recessive dystrophic epidermolysis bullosa. J Dermatol Sci. 2006;42:241–8.

    Article  CAS  PubMed  Google Scholar 

  119. Alcántara-Ortigoza MÁ, Belmont-Martínez L, Vela-Amieva M, González-Del AA. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay. Genet Test. 2008;12:409–14.

    Article  PubMed  Google Scholar 

  120. Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, et al. CTNS mutations in an American-based population of cystinosis patients. Am J Hum Genet. 1998;63:1352–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Rodríguez-Pombo P, Navarrete R, Merinero B, Gómez-Puertas P, Ugarte M. Mutational spectrum of maple syrup urine disease in Spain. Hum Mutat. 2006;27:715.

    Article  PubMed  Google Scholar 

  122. Tsuruta M, Mitsubuchi H, Mardy S, Miura Y, Hayashida Y, Kinugasa A, et al. Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain α-keto acid dehydrogenase complex. J Hum Genet. 1998;43:91–100.

    Article  CAS  PubMed  Google Scholar 

  123. Ellingson M.S, Wick M.J, White W.M, Raymond K.M, SaengeR A.K, Pichurin P.N et al. Pregnancy in an individual with mild Smith-Lemli-Opitz syndrome. Clin Genet. 2014;85:495–497.

  124. Patrono C, Dionisi-Vici C, Giannotti A, Bembi B, Digilio MC, Rizzo C, et al. Two novel mutations of the human Δ7-sterol reductase (DHCR7) gene in children with Smith-Lemli-Opitz syndrome. Mol Cell Probes. 2002;16:315–8.

    Article  CAS  PubMed  Google Scholar 

  125. DaRe JT, Vasta V, Penn J, Tran NTB, Hahn SH. Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity. BMC Med Genet. 2013;14:1.

    Article  Google Scholar 

  126. Arranz JA, Piñol F, Kozak L, Pérez-Cerdá C, Cormand B, Ugarte M, et al. Splicing mutations, mainly IVS6.1 (G>T), account for 70% of fumarylacetoacetate hydrolase (FAH) gene alterations, including 7 novel mutations, in a survey of 29 tyrosinemia type I patients. Hum Mutat. 2002;20:180–8.

  127. Boito CA, Melacini P, Vianello A, Prandini P, Gavassini BF, Bagattin A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol. 2005;62:1894–9.

    Article  PubMed  Google Scholar 

  128. Rosales XQ, Moser SJ, Tran T, McCarthy B, Dunn N, Habib P, et al. Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I. J Cardiovasc Magn Reson. 2011;13:39.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Marks PA, Banks J, Gross RT. Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency. Nature. 1962;194:454–6.

    Article  CAS  Google Scholar 

  130. Cittadella R, Civitelli D, Manna I, Azzia N, Cataldo A, Schiliroa G, et al. Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency in south-east Sicily. Ann Hum Genet. 1997;61:229–34.

    Article  CAS  PubMed  Google Scholar 

  131. Sáenz GF, Chaves M, Berrantes A, Elizondo J, Montero AG, Yoshida A. A glucose-6-phosphate dehydrogenase variant, gd(-) santamaria found in costa rica1. Acta Haematol. 1984;72:37–40.

    Article  PubMed  Google Scholar 

  132. Gómez-Manzo S, Marcial-Quino J, Vanoye-Carlo A, Enríquez-Flores S, De la Mora-De la Mora I, González-Valdez A, et al. Mutations of glucose-6-phosphate dehydrogenase durham, Santa-Maria and A+ variants are associated with loss functional and structural stability of the protein. Int J Mol Sci. 2015;16:28657–68.

  133. Gort L, Coll MJ, Chabás A. Glycogen storage disease type II in Spanish patients: high frequency of c.1076–1G>C mutation. Mol Genet Metab. 2007;92:183–7.

  134. Musumeci O, Catalano N, Barca E, Ravaglia S, Fiumara A, Gangemi G, et al. Auditory system involvement in late onset Pompe disease: a study of 20 Italian patients. Mol Genet Metab. 2012;107:480–4.

    Article  CAS  PubMed  Google Scholar 

  135. Luzi P, Rafi MA, Wenger DA. Multiple mutations in the GALC gene in a patient with adult-onset Krabbe disease. Ann Neurol. 1996;40:116–9.

    Article  CAS  PubMed  Google Scholar 

  136. Shao YH, Choquet K, La Piana R, Tétreault M, Dicaire MJ, Boycott KM, et al. Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia. Neurogenetics. 2016;17:137–41.

    Article  CAS  PubMed  Google Scholar 

  137. Orsini JJ, Kay DM, Saavedra-Matiz CA, Wenger DA, Duffner PK, Erbe RW, et al. Newborn screening for Krabbe disease in New York State: the first eight years’ experience. Genet Med. 2016;18:239–48.

    Article  CAS  PubMed  Google Scholar 

  138. Yamada N, Fukuda S, Tomatsu S, Muller V, Hopwood JJ, Nelson J, et al. Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype. Hum Mutat. 1998;11:202–8.

    Article  CAS  PubMed  Google Scholar 

  139. Tomatsu S, Nishioka T, Montaño AM, Gutierrez MA, Pena OS, Orii KO, et al. Mucopolysaccharidosis IVA: identification of mutations and methylation study in GALNS gene. J Med Genet. 2004;41:1–6.

    Article  Google Scholar 

  140. Pajares S, Alcalde C, Couce ML, Del Toro M, González-Meneses A, Guillén E, et al. Molecular analysis of mucopolysaccharidosis IVA (Morquio A) in Spain. Mol Genet Metab. 2012;106:196–201.

    Article  CAS  PubMed  Google Scholar 

  141. Pintos-Morell G, Blasco-Alonso J, Couce ML, Gutiérrez-Solana LG, Guillén-Navarro E, O’Callaghan M, et al. Elosulfase alfa for mucopolysaccharidosis type IVA: real-world experience in 7 patients from the Spanish Morquio—a early access program. Mol Genet Metab Reports. 2018;15:116–20.

    Article  CAS  Google Scholar 

  142. Gort L, Boleda MD, Tyfield L, Vilarinho L, Rivera I, Cardoso ML, et al. Mutational spectrum of classical galactosaemia in Spain and Portugal. J Inherit Metab Dis. 2006;29:739–42.

    Article  CAS  PubMed  Google Scholar 

  143. Stone DL, Tayebi N, Orvisky E, Stubblefield B, Madike V, Sidransky E. Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease. Hum Mutat. 2000;15:181–8.

    Article  CAS  PubMed  Google Scholar 

  144. Filocamo M, Grossi S, Stroppiano M, Regis S, Tortori-Donati P, Allegri A, et al. Homozygosity for a non-pseudogene complex glucocerebrosidase allele as cause of an atypical neuronopathic form of Gaucher disease. Am J Med Genet. 2005;134 A:95–6.

  145. Busquets C, Merinero B, Christensen E, Gelpí JL, Campistol J, Pineda M, et al. Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct. Pediatr Res. 2000;48:315–22.

    Article  CAS  PubMed  Google Scholar 

  146. Gandía M, del Castillo FJ, Rodríguez-Álvarez FJ, Garrido G, Villamar M, Calderón M, et al. A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing impairment. PLoS ONE. 2013;8:1–9.

    Article  Google Scholar 

  147. Gualandi F, Ravani A, Berto A, Sensi A, Trabanelli C, Falciano F, et al. Exploring the clinical and epidemiological complexity of GJB2-linked deafness. Am J Med Genet. 2002;112:38–45.

    Article  CAS  PubMed  Google Scholar 

  148. Rabionet R, Zelante L, López-Bigas N, D’Agruma L, Melchionda S, Restagno G, et al. Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. Hum Genet. 2000;106:40–4.

    CAS  PubMed  Google Scholar 

  149. Amorini M, Romeo P, Bruno R, Galletti F, Di Bella C, Longo P, et al. Prevalence of deafness-associated connexin-26 (GJB2) and connexin-30 (GJB6) pathogenic alleles in a large patient cohort from Eastern Sicily. Ann Hum Genet. 2015;79:341–9.

    Article  CAS  PubMed  Google Scholar 

  150. Cryns K, Orzan E, Murgia A, Huygen PLM, Moreno F, Del Castillo I, et al. A genotype-phenotype correlation for GJB2 (connexin 26) deafness. J Med Genet. 2004;41:147–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Silva CMD, Severini MH, Sopelsa A, Coelho JC, Zaha A, D’Azzo A, et al. Six novel β-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis. Hum Mutat. 1999;13:401–9.

    Article  CAS  PubMed  Google Scholar 

  152. Gort L, Santamaria R, Grinberg D, Vilageliu, Chabás A. Identification of a novel pseudodeficiency allele in the GLB1 gene in a carrier of GM1 gangliosidosis. Clin Genet. 2007;72:109–11.

  153. Santamaria R, Chabás A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006;27:1060.

  154. Huang Z, Sun Y, Fan Y, Wang L, Liu H, Gong Z, et al. Genetic evaluation of 114 Chinese short stature children in the next generation era: a single center study. Cell Physiol Biochem. 2018;49:295–305.

    Article  CAS  PubMed  Google Scholar 

  155. Fernández-Marmiesse A, Morey M, Pineda M, Eiris J, Couce ML, Castro-Gago M, et al. Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders. Orphanet J Rare Dis. 2014;9.

  156. Brunner-Agten S, Hergersberg M, Herklotz R, Hirt A, Huber AR. Compound heterozygosity of Hb Hamilton and de novo mutated HbM Saskatoon. Ann Hematol. 2010;89:517–8.

    Article  PubMed  Google Scholar 

  157. Eng B, Chui DHK, Saunderson J, Olivieri NF, Waye JS. Identification of two novel β°-thalassemia mutations in a filipino family: frameshift codon 67 (− TG) and a β-globin gene deletion. Hum Mutat. 1993;2:375–9.

    Article  CAS  PubMed  Google Scholar 

  158. Inglehearn C, Farrart J, Denton M, Gal A, Humphriest SP, Bhattacharya S. Extensive genetic heterogeneity in autosomal dominant retinitis pigmentosa. J Hum Genet. 1993;53:537–9.

    Google Scholar 

  159. Tang NLS, Hui J, Yong CKK, Wong LTK, Applegarth DA, Vallance HD, et al. A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. Clin Biochem. 2003;36:145–9.

    Article  CAS  PubMed  Google Scholar 

  160. Philip L P, Keith H, J C, Colleen L M, Yuezhou Y, Donald T. Partial pyridoxine responsiveness in PNPO deficiency. JIMD Rep. 2012;4:113–6.

  161. Ozgul RK, Karaca M, Kilic M, Kucuk O, Yucel-Yilmaz D, Unal O, et al. Phenotypic and genotypic spectrum of turkish patients with isovaleric acidemia. Eur J Med Genet. 2014;57:596–601.

    Article  PubMed  Google Scholar 

  162. Mohsen AA, Anderson BD, Volchenboum SL, Battaile KP, Tiffany K, Roberts D, et al. Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemia. Biochemistry. 1998;2960:10325–35.

    Article  Google Scholar 

  163. Fonseca H, Azevedo L, Serrano C, Sousa C, Marcão A, Vilarinho L. 3-Methylcrotonyl-CoA carboxylase deficiency: mutational spectrum derived from comprehensive newborn screening. Gene. 2016;594:203–10.

    Article  CAS  PubMed  Google Scholar 

  164. Grünert SC, Stucki M, Morscher RJ, Suormala T, Bürer C, Burda P, et al. 3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals. Orphanet J Rare Dis. 2012;7.

  165. Cekin N, Akyurek ME, Pinarbasi E, Ozen F. MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever. Gene. 2017;626:9–13.

    Article  CAS  PubMed  Google Scholar 

  166. Gumus E. The frequency of MEFV gene mutations and genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by using next generation sequencing and report of a novel exon 4 mutation (I423T). J Clin Med. 2018;7:105.

    Article  PubMed Central  Google Scholar 

  167. Timmann C, Muntau B, Kuhne K, Gelhaus A, Horstmann RD. Two novel mutations R653H and E230K in the Mediterranean fever gene associated with disease. Mutat Res - Fundam Mol Mech Mutagen. 2001;479:235–9.

    Article  CAS  Google Scholar 

  168. Kallinich T, Wittkowski H, Keitzer R, Roth J, Foell D. Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever. Ann Rheum Dis. 2010;69:677–82.

    Article  CAS  PubMed  Google Scholar 

  169. Brasil S, Rachard E, Finnigan AJ, Leal F, Merinero B, Banerjee R, et al. Methylmalonic acidura cbIB type: characterization of two novel mutations and mitochondrial dysfunction studies. Clin Genet. 2015;87:576–81.

    Article  CAS  PubMed  Google Scholar 

  170. Adato A, Weil D, Kalinski H, Pel-Or Y, Ayadi H, Petit C, et al. Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins. J Hum Genet. 1997;61:813–21.

    Article  CAS  Google Scholar 

  171. Riazuddin S, Nazli S, Ahmed ZM, Yang Y, Zulfiqar F, Shaikh RS, et al. Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function. Hum Mutat. 2008;29:502–11.

    Article  CAS  PubMed  Google Scholar 

  172. Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, et al. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients. Eur J Hum Genet. 2016;24:1730–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Miné, Manuèle; Chen J, Desguerre I, Marchant D, Abitbol M, Ricquier D, Lonlay P De, et al. A large genomic deletion in the PDHX gene caused by the retrotranspositional insertion of a full-length LINE-1 element. Hum Mutat. 2006;0:1–6.

  174. Savarese M, Di Fruscio G, Mutarelli M, Torella A, Magri F, Santorelli FM, et al. MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples. Acta Neuropathol Commun. 2014;2.

  175. Kaminski WE, Klünemann HH, Ibach B, Aslanidis C, Klein HE, Schmitz G. Identification of novel mutations in the NPC1 gene in German patients with Niemann-Pick C disease. J Inherit Metab Dis. 2002;25:385–9.

    Article  CAS  PubMed  Google Scholar 

  176. Rodríguez-Quiroga SA lejandr., Cordoba M, González-Morón D, Medina N, Vega P, Dusefante CV azque., et al. Neurogenetics in Argentina: diagnostic yield in a personalized research based clinic. Genet Res. 2015;97:e10.

  177. Fernandez-Valero EM, Ballart A, Iturriaga C, Lluch M, Macias J, Vanier MT, et al. Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations. Clin Genet. 2005;68:245–54.

    Article  CAS  PubMed  Google Scholar 

  178. Sun X, Marks DL, Park WD, Wheatley CL, Puri V, O’Brien JF, et al. Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1. Am J Hum Genet. 2001;68:1361–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Fancello T, Dardis A, Rosano C, Tarugi P, Tappino B, Zampieri S, et al. Molecular analysis of NPC1 and NPC2 gene in 34 Niemann-Pick C Italian patients: identification and structural modeling of novel mutations. Neurogenetics. 2009;10:229–39.

    Article  CAS  PubMed  Google Scholar 

  180. Sheth JJ, Sheth FJ, Oza N. Niemann-Pick type C disease. Indian Pediatr. 2008;45:505–7.

    PubMed  Google Scholar 

  181. Romanello M, Zampieri S, Bortolotti N, Deroma L, Sechi A, Fiumara A, et al. Comprehensive evaluation of plasma 7-ketocholesterol and cholestan-3β,5α,6β-triol in an Italian cohort of patients affected by Niemann-Pick disease due to NPC1 and SMPD1 mutations. Clin Chim Acta. 2016;455:39–45.

    Article  CAS  PubMed  Google Scholar 

  182. Dvorakova L, Sikora J, Hrebicek M, Hulkova H, Bouckova M, Stolnaja L, et al. Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder? J Inherit Metab Dis. 2006;29:591.

  183. Mallolas J, Vilaseca MA, Campistol J, Lambruschini N, Cambra FJ, Estivill X, et al. Mutational spectrum of phenylalanine hydroxylase deficiency in the population resident in Catalonia: genotype-phenotype correlation. Hum Genet. 1999;105:468–73.

    Article  CAS  PubMed  Google Scholar 

  184. Hennermann JB, Vetter B, Wolf C, Windt E, Bührdel P, Seidel J, et al. Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations. Hum Mutat. 2000;15:254–60.

    Article  CAS  PubMed  Google Scholar 

  185. Liang Y, Huang MZ, Cheng CY, Chao HK, Fwu VT, Chiang SH, et al. The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population. J Hum Genet. 2014;59:145–52.

    Article  CAS  PubMed  Google Scholar 

  186. Tao J, Li N, Jia H, Liu Z, Li X, Song J, et al. Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria. Pediatr Res. 2015;78:691–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Liu N, Huang Q, Li Q, Zhao D, Li X, Cui L, et al. Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China. BMC Med Genet BMC Medical Genetics. 2017;18:1–7.

    Google Scholar 

  188. Hoenicka J, Muro S, Pe C, Richard E, Desviat LR, Ugarte M. Human propionyl-CoA carboxylase b subunit gene: exon-intron propionic acidemia patients. Am J Hum Genet. 1998;63:360–9.

    Article  PubMed  PubMed Central  Google Scholar 

  189. Chloupkova M, Maclean KN, Alkhateeb A, Kraus JP. Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes expressed in Escherichia coli. Hum Mutat. 2002;19:629–40.

    Article  CAS  PubMed  Google Scholar 

  190. Pérez B, Desviat LR, Rodríguez-Pombo P, Clavero S, Navarrete R, Perez-Cerdá C, et al. Propionic acidemia: identification of twenty-four novel mutations in Europe and North America. Mol Genet Metab. 2003;78:59–67.

    Article  PubMed  Google Scholar 

  191. Xu Y, Guan L, Xiao X, Zhang J, Li S, Jiang H, et al. Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing. Mol Vis. 2015;21:477–86.

    PubMed  PubMed Central  Google Scholar 

  192. Sloan-Heggen CM, Bierer AO, Shearer AE, Kolbe DL, Nishimura CJ, Frees KL, et al. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum Genet. 2016;135:441–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Perreault-Micale C, Frieden A, Kennedy CJ, Neitzel D, Sullivan J, Faulkner N, et al. Truncating variants in the majority of the cytoplasmic domain of pcdh15 are unlikely to cause Usher syndrome 1F. J Mol Diagnostics. 2014;16:673–8.

    Article  CAS  Google Scholar 

  194. Bergmann C, Senderek J, Windelen E, Küpper F, Middeldorf I, Schneider F, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005;67:829–48.

    Article  CAS  PubMed  Google Scholar 

  195. Schneider F, Dornia C, Bergmann C, Senderek J, Ku F, Kirfel J, et al. PKHD1 mutations in autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat. 2004;463:453–63.

    Google Scholar 

  196. Furu L, Onuchic LF, Gharavi ALI, Hou X, Esquivel EL, Nagasawa Y, et al. Milder presentation of recessive polycystic kidney disease requires presence of amino acid substitution mutations. J Am Soc Nephrol. 2014;2004–14.

  197. Gunay-Aygun M, Font-montgomery E, Lukose L, Tuchman M, Graf J, Bryant JC, et al. Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease. Clin J Am Soc Nephrol. 2010;1–13.

  198. Sharp AM, Messiaen LM, Page G, Antignac C, Gubler M, Onuchic LF, et al. Comprehensive genomic analysis of PKHD1 mutations in key points. Clin J Am Soc Nephrol. 2005;336–49.

  199. Melchionda S, Palladino T, Castellana S, Giordano M, Benetti E, De BP, et al. Expanding the mutation spectrum in 130 probands with ARPKD: identification of 62 novel PKHD1 mutations by sanger sequencing and MLPA analysis. Nat Publ Group. 2016;61:811–21.

    CAS  Google Scholar 

  200. Teneiji A Al, Bruun TUJ, Sidky S, Cohn RD, Mendoza-londono R, Moharir M, et al. Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II. Mol Genet Metab. 2016.

  201. Ávila-Fernández A, Cantalapiedra D, Aller E, Vallespín E, Aguirre-lambán J, Blanco-kelly F, et al. Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray. Mol Vis. 2010;2550–8.

  202. Consugar MB, Navarro-gomez D, Place EM, Kinga M, Sousa ME, Fonseca-kelly ZD, et al. Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible and more sensitive for variant detection than exome sequencing. Genet Med. 2016;17:253–61.

    Article  Google Scholar 

  203. Thompson DA, Janecke AR, Lange J, Feathers KL, Mchenry CL, Stockton DW, et al. Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle. Hum Mol Genet. 2005;14:3865–75.

    Article  CAS  PubMed  Google Scholar 

  204. Muschol N, Pohl S, Meyer A, Gal A, Ullrich K, Braulke T. Residual activity and proteasomal degradation of p. Ser298Pro sulfamidase identified in patients with a mild clinical phenotype of Sanfilippo A syndrome. Am J Med Genet A. 2011;1634–9.

  205. Mikaeloff Y, Froissart R, Caridade G, Caillaud C, Levade T, Chabrol B, et al. Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med Genet A. 2010;58–68.

  206. Beesley C E, Young E P, Vellodi A, Winchester B G. Mutational analysis of Sanfilippo syndrome type A (MPS IIIA): identification of 13 novel mutations. Genet AJM. 1997;704–7.

  207. Pera A, Villamar M, Viñuela A, Gandía M, Medà C, Moreno F, et al. A mutational analysis of the SLC26A4 gene in Spanish hearing-impaired families provides new insights into the genetic causes of Pendred syndrome and DFNB4 hearing loss. Eur J Hum Genet. 2008;16:888–96.

    Article  CAS  PubMed  Google Scholar 

  208. Bademci G, Mahdieh N, Bonyadi M, Duman D, Cengiz FB, Menendez I, et al. Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort. Genet Med. 2016;18:364–71.

    Article  CAS  PubMed  Google Scholar 

  209. Wolf ÃA, Frohne A, Allen M, Parzefall T, Koenighofer M, Schreiner MM, et al. A novel mutation in SLC26A4 causes nonsyndromic autosomal recessive hearing impairment. Otol Neurotol. 2016;173–9.

  210. Simonaro CM, Desnick RJ, Mcgovern MM, Wasserstein MP, Schuchman EH. The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations. Am J Hum Genet. 2002;1413–9.

  211. Manshadi MD, Kamalidehghan B, Keshavarzi F. Four novel p.N385K , p.V36A, c.1033–1034insT and c.1417–1418delCT mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene in patients with types A and B Niemann-Pick disease (NPD). 2015;1:6668–76.

  212. Gucev Z, Tasic V, Pop-jordanova N, Schuchmann EH. Two siblings with Niemann-Pick disease (NPD) type B : clinical findings and novel mutations of the acid sphingomyelinase gene. Indian J Pediatr. 2013;80:163–4.

    Article  PubMed  Google Scholar 

  213. Mei X, Xia O, Xia J, Verpy E, Lin L, Arti D, et al. Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness. Hum Genet. 2002;26–30.

  214. Haddad M, Guys JM, Reynaud R, Alessandrini P, Wagner K, Ste J, et al. Minor hypospadias: the “tip of the iceberg” of the partial androgen insensitivity syndrome. PLoS One. 2013;8.

  215. Akcay T, Fernandez-cancio M, Turan S, G T. AR and SRD5A2 gene mutations in a series of 51 Turkish 46, XY DSD children with a clinical diagnosis of androgen insensitivity. Andrology. 2014;2:572–8,

  216. Strauss KA, Mazariegos G V, Sindhi R. Elective liver transplantation for the treatment of classical maple syrup urine disease. Am J Transplant. 2006;557–64.

  217. Schiff M, Froissart R, Olsen RKJ, Acquaviva C, Vianey-saban C. Electron transfer X avoprotein de W ciency: functional and molecular aspects. Mol Genet Metab. 2006;88:153–8.

    Article  CAS  PubMed  Google Scholar 

  218. Slaoui M, Ferrandiz D, Gautier P, Costa C, Costa JM. Factor VIII (FVIII) gene mutations in 120 patients with hemophilia A : detection of 26 novel mutations and correlation with FVIII inhibitor development. J Thromb Haemost. 2007;1469–76.

  219. Santacroce R, Acquila M, Belvini D, Castaldo G, Garagiola I, Giacomelli S.H, et al. Identification of 217 unreported mutations in the F8 gene in a group of 1, 410 unselected Italian patients with hemophilia A. J Hum Genet. 2008;275–84.

  220. Fernández-López O, García-Lozano J-R, Núñez-Vázquez R, Pérez-Garrido R, Núñez-Roldán A. The spectrum of mutations in southern spanish patients with hemophilia A and identification of 28 novel mutations. Haemat. 2005;90:707–10.

    Google Scholar 

  221. David D, Ventura C, Moreira I, Diniz MJ, Antunes M, Tavares A, Araújo F, Morais S, Campos M, Lavinha J, Kemball-Cook G. The spectrum of mutations and molecular pathogenesis of hemophilia a in 181 portuguese patients. Haemat. 2006;91:840–3.

    CAS  Google Scholar 

  222. http://www.factorix.org/advance_search_results.php?dosearch=1&codon=323

  223. Okano Y, Asada M, Fujimoto A, Ohtake A, Murayama K, Hsiao K. J., el at. A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, “Osaka,” in Asians. J Hum Genet. 2001;68:1036–1042.

  224. Branton M.H, Schiffmann R, Sabnis S.G, Murray G.J, Quirk J.M, Altarescu G, et al. Natural history of fabry renal disease influence of galactosidase A activity and genetic mutations on clinical course. 2002;81:122–38

  225. Boutron A, Acquaviva C, Vianey-saban C, De LP, De BHO, Guffon N, et al. Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency. Mol Genet Metab. 2011;103:341–8.

    Article  CAS  PubMed  Google Scholar 

  226. Shon Y.B, Ki C-S, Kim C-H, Ko A-R, Yook Y-J, Lee S-J, et al. Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II. Clin Genet. 2012;185–90.

  227. Saini AG, Sankhyan N, Singhi PSC. Chorea in late-infantile neuronal ceroid lipofuscinosis: an atypical presentation. Pediatr Neurol. 2016;60:75–8.

    Article  PubMed  Google Scholar 

  228. Wang J, Zhang VW, Feng Y, Tian X, Li F, Truong C, et al. Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2015;55:6213–23.

    Article  Google Scholar 

  229. Riera M, Navarro R, Ruiz-nogales S, Méndez P, Burés-jelstrup A, Corcóstegui B, et al. Whole exome sequencing using ion proton system enables reliable genetic diagnosis of inherited retinal dystrophies. Nat Publ Gr. 2017;1–13.

  230. Xu Y, Guan L, Shen T, Zhang J, Xiao X, Jiang H. Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing. Hum Genet. 2014;1255–71.

  231. Sun T, Xu K, Ren Y, Xie Y, Zhang X, Tian L, et al. Comprehensive molecular screening in Chinese Usher syndrome patients. Invest Ophthalmol Vis Sci. 2018;59:1229–37.

    Article  CAS  PubMed  Google Scholar 

  232. Wang F, Wang H, Tuan H, Nguyen DH, Sun V, Keser V, et al. Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements. Hum Genet. 2015;133:331–45.

    Article  Google Scholar 

  233. Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-juan A, Hull S, et al. Comprehensive rare variant analysis via whole-genome sequencing to determine the molecular pathology of inherited retinal disease. J Hum Genet. 2017;75–90.

  234. Appelt S, Heinrich V, Krawitz PM, Schiska D, Kru U, Parkhomchuk D, et al. Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome. Mol Genet Genomic Med. 2014;393–401.

  235. Lenassi E, Vincent A, Li Z, Saihan Z, Coffey AJ, Steele-stallard HB, et al. A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants. Eur J Hum Genet. 2015;1318–27.

  236. García-García G, Aller E, Jaijo T, Aparisi MJ, Larrieu L, Faugère V, et al. Novel deletions involving the USH2A gene in patients with Usher syndrome and retinitis pigmentosa. Mol Vis. 2014;106:1398–410.

    Google Scholar 

  237. Ge Z, Bowles K, Goetz K, Scholl HPN, Wang F, Wang X, et al. NGS-based molecular diagnosis of 105 eyeGENE ® probands with retinitis pigmentosa. Nat Publ Gr. 2015;1–9.

  238. Sun W, Huang L, Xu Y, Xiao X, Li S, Jia X, et al. Exome sequencing on 298 probands with early-onset high myopia: approximately one-fourth show potential pathogenic mutations in RetNet genes. Invest Ophthalmol Vis Sci. 2015;56:8365–72.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. CEIFER Biobanco - NextClinics, Calle Maestro Bretón, 1, 18004, Granada, Spain

    Marta Molina Romero, Alberto Yoldi Chaure, José Luis del Pico Sánchez, Ángel Vaquero Argüelles, Juan Pablo Ramírez López & José Antonio Castilla Alcalá

  2. CEIFER Biobanco - NextClinics, Sevilla, Spain

    Miguel Gañán Parra & Paloma de la Fuente Vaquero

  3. CEIFER Biobanco - NextClinics, Córdoba, Spain

    Purificación Navas Bastida

  4. U. Reproducción, UGC Obstetricia y Ginecología, HU Virgen de Las Nieves, Granada, Spain

    José Antonio Castilla Alcalá

  5. Instituto de Investigación Biosanitaria Ibs.Granada, Granada, Spain

    José Antonio Castilla Alcalá

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  1. Marta Molina Romero
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Conceptualisation, M.M.R. and JA.C.A.; data analysis, M.M.R., JL.P.S., A.Y.C., M.G.P., P.N.B., A.V.A., P.F.V. and JA.C.A.; original draft preparation, M.M.R., JP.R.L. and JA.C.A.; review and editing M.M.R., A.Y.C., JP.R.L. and JA.C.A. All authors have revised and agreed upon the final version of the manuscript.

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Molina Romero, M., Yoldi Chaure, A., Gañán Parra, M. et al. Probability of high-risk genetic matching with oocyte and semen donors: complete gene analysis or genotyping test?. J Assist Reprod Genet 39, 341–355 (2022). https://doi.org/10.1007/s10815-021-02381-0

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