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Prospect in Pediatric Diseases Medicine pp 1–9Cite as

Application of Array Comparative Genomic Hybridization in Newborns with Multiple Congenital Anomalies

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Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 912))

Abstract

Major congenital anomalies are detectable in 2–3 % of the newborn population. Some of their genetic causes are attributable to copy number variations identified by array comparative genomic hybridization (aCGH). The value of aCGH screening as a first-tier test in children with multiple congenital anomalies has been studied and consensus adopted. However, array resolution has not been agreed upon, specifically in the newborn or infant population. Moreover, most array studies have been focused on mixed populations of intellectual disability/developmental delay with or without multiple congenital anomalies, making it difficult to assess the value of microarrays in newborns. The aim of the study was to determine the optimal quality and clinical sensitivity of high-resolution array comparative genomic hybridization in neonates with multiple congenital anomalies. We investigated a group of 54 newborns with multiple congenital anomalies defined as two or more birth defects from more than one organ system. Cytogenetic studies were performed using OGT CytoSure 8 × 60 K microarray. We found ten rearrangements in ten newborns. Of these, one recurrent syndromic microduplication was observed, whereas all other changes were unique. Six rearrangements were definitely pathogenic, including one submicroscopic and five that could be seen on routine karyotype analysis. Four other copy number variants were likely pathogenic. The candidate genes that may explain the phenotype were discussed. In conclusion, high-resolution array comparative hybridization can be applied successfully in newborns with multiple congenital anomalies as the method detects a significant number of pathogenic changes, resulting in early diagnoses. We hypothesize that small changes previously considered benign or even inherited rearrangements should be classified as potentially pathogenic at least until a subsequent clinical assessment would exclude a developmental delay or dysmorphism.

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References

  • Carroll TJ, Park J-S, Hayashi S, Majumdar A, McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell 9:283–292

    Article  CAS  PubMed  Google Scholar 

  • CDC (2008) Centers for Disease Control and prevention. Update on overall prevalence of major birth defects-Atlanta, Georgia, 1978–2005. Morb Mortal Wkly Rep 57:1–5

    Google Scholar 

  • Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P (2010) Origins and functional impact of copy number variation in the human genome. Nature 464:704–712

    Article  CAS  PubMed  Google Scholar 

  • Crotwell PL, Hoyme HE (2012) Advances in whole-genome genetic testing: from chromosomes to microarrays. Curr Probl Pediatr Adolesc Health Care 42:47–73

    Article  PubMed  Google Scholar 

  • Eto K, Sakai N, Shimada S, Shioda M, Ishigaki K, Hamada Y, Shinpo M, Azuma J, Tominaga K, Shimojima K, Ozono K, Osawa M, Yamamoto T (2013) Microdeletions of 3p21.31 characterized by developmental delay, distinctive features, elevated serum creatine kinase levels, and white matter involvement. Am J Med Genet 161A:3049–3056

    Article  PubMed  Google Scholar 

  • Eudy JD, Pickering DL, Lutz R, Platt K, Dave BJ, Olney AH, Sanger WG (2010) 18q22.3 – > 18q23 deletion syndrome and cleft palate. Am J Med Genet A 152A:1046–1048

    Article  PubMed  Google Scholar 

  • Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, Van Vooren S, Moreau Y, Pettett RM, Carter NP (2009) DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Am J Hum Genet 84:524–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldmuntz E, Lin A (2008) Genetics of congenital heart defects. In: Allen HD, Driscoll DJ, Feltes TF, Shaddy RE (eds) Moss and Adams’ heart disease in infants, children and adolescents, vol 1. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, pp 545–572

    Google Scholar 

  • Janssen R, Distelmaier F, Smeets R, Wijnhoven T, Østergaard E, Jaspers NG, Raams A, Kemp S, Rodenburg RJ, Willems PH, van den Heuvel LP, Smeitink JA, Nijtmans LG (2009) Contiguous gene deletion of ELOVL7, ERCC8 and NDUFAF2 in a patient with a fatal multisystem disorder. Hum Mol Genet 18:3365–3374

    Article  CAS  PubMed  Google Scholar 

  • Koyano-Nakagawa N, Nishida J, Baldwin D, Arai K, Yokota T (1994) Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin-3 promoter. Mol Cell Biol 14:5099–5107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu X-Y, Phung MT, Shaw CA, Pham K, Neil SE, Patel A, Sahoo T, Bacino CA, Stankiewicz P, Kang SH, Lalani S, Chinault AC, Lupski JR, Cheung SW, Beaudet AL (2008) Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics 122:1310–1318

    Article  PubMed  PubMed Central  Google Scholar 

  • Materna-Kiryluk A (2014) Multiple congenital anomalies. In: Materna-Kiryluk A (ed) Polish registry of congenital malformations. Poznan Medical University, Poznan, pp 153–154

    Google Scholar 

  • Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM (2010) Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86:749–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ming JE, Geiger E, James AC, Ciprero KL, Nimmakayalu M, Zhang Y, Huang A, Vaddi M, Rappaport E, Zackai EH, Shaikh TH (2006) Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays. Hum Mutat 27:467–473

    Article  CAS  PubMed  Google Scholar 

  • Mitchison HM, Schmidts M, Loges NT, Freshour J, Dritsoula A, Hirst RA, O’Callaghan C, Blau H, Al Dabbagh M, Olbrich H, Beales PL, Yagi T, Mussaffi H, Chung EMK, Omran H, Mitchell DR (2012) Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet 44:381–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niemann S, Zhao C, Pascu F, Stahl U, Aulepp U, Niswander L, Weber JL, Müller U (2004) Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family. Am J Hum Genet 74:558–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reddy K, Zamiri B, Stanley SY, Macgregor RB Jr, Pearson CE (2013) The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures. J Biol Chem 288:9860–9866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JPT, Burton H (2009) Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies of 13,926 subjects. Genet Med 11:139–146

    Article  CAS  PubMed  Google Scholar 

  • Sakakibara S, Nakamura Y, Satoh H, Okano H (2001) RNA-binding protein Musashi2: developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS. J Neurosci 21:8091–8107

    CAS  PubMed  Google Scholar 

  • Stankiewicz P, Beaudet AL (2007) Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr Opin Genet Dev 17:182–192

    Article  CAS  PubMed  Google Scholar 

  • Szczałuba K, Nowakowska BA, Sobecka K, Smyk M, Castaneda J, Dudkiewicz Z, Kutkowska-Kaźmierczak A, Sąsiadek MM, Śmigiel R, Bocian E (2015) High-resolution array comparative genomic hybridization utility in Polish newborns with isolated cleft lip and palate. Neonatology 107:173–178

    Article  PubMed  Google Scholar 

  • Tzschach A, Krause-Plonka I, Menzel C, Kalscheuer V, Toennies H, Scherthan H, Knoblauch A, Radke M, Ropers HH, Hoeltzenbein M (2006) Molecular cytogenetic analysis of a de novo interstitial deletion of 5q23.3q31.2 and its phenotypic consequences. Am J Med Genet 140:496–502

    Article  PubMed  Google Scholar 

  • Wentzel C, Fernstrom M, Ohrner Y, Anneren G, Thuresson AC (2008) Clinical variability of the 22q11.2 duplication syndrome. Eur J Med Genet 51:501–510

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financed by the Polish National Science Center grant no. N N407 459438 in the years 2010–2013.

Competing Interests

The authors declare no competing interests in relation to this article.

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Authors and Affiliations

  1. Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland

    Krzysztof Szczałuba, Beata Nowakowska, Katarzyna Sobecka, Marta Smyk, Jennifer Castaneda, Jakub Klapecki, Anna Kutkowska-Kaźmierczak & Ewa Bocian

  2. Department of Genetics, Wroclaw Medical University, Wroclaw, Poland

    Robert Śmigiel

  3. Department of Social Pediatrics, Wroclaw Medical University, Wroclaw, Poland

    Robert Śmigiel

  4. Department of Immunopathology of Infectious and Parasitic Diseases, Warsaw Medical University, Warsaw, Poland

    Marek Radkowski

  5. Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland

    Urszula Demkow

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  1. Krzysztof Szczałuba
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  2. Beata Nowakowska
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  3. Katarzyna Sobecka
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  4. Marta Smyk
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  7. Anna Kutkowska-Kaźmierczak
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  8. Robert Śmigiel
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  9. Ewa Bocian
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  11. Urszula Demkow
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Correspondence to Krzysztof Szczałuba .

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Editors and Affiliations

  1. Institute of Nursing, PublicHigher Medical Professional School Institute of Nursing, Opole, Poland

    Mieczyslaw Pokorski

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Szczałuba, K. et al. (2016). Application of Array Comparative Genomic Hybridization in Newborns with Multiple Congenital Anomalies. In: Pokorski, M. (eds) Prospect in Pediatric Diseases Medicine. Advances in Experimental Medicine and Biology(), vol 912. Springer, Cham. https://doi.org/10.1007/5584_2016_235

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