Absence of WNT4 gene mutation in a patient with MURCS association

Zohreh Shoar; Tapan Ganguly; Carol E. Anderson; Francesco De Luca; Elizabeth Suarez

doi:10.1515/jpem-2013-0335

Published by De Gruyter December 19, 2013

Absence of WNT4 gene mutation in a patient with MURCS association

Zohreh Shoar , Tapan Ganguly , Carol E. Anderson , Francesco De Luca and Elizabeth Suarez

From the journal Journal of Pediatric Endocrinology and Metabolism

https://doi.org/10.1515/jpem-2013-0335

Showing a limited preview of this publication:

Abstract

MURCS (Mullerian duct aplasia, Renal anomalies, and Cervicothoracic Somite dysplasia) association is a group of congenital genito-urinary and skeletal malformations. We report an adolescent girl with the cardinal features of MURCS association, obesity, and clinical findings of hyperandrogenism who did not show any exonic mutation of the WNT4 gene. Our finding excludes WNT4 gene as a candidate for MURCS association and suggests the need for further genetic studies.

Keywords: female genitalia; female reproductive system; hyperandrogenism; MURCS association; WNT4 gene

Corresponding author: Zohreh Shoar, MD, MPH, Section of Pediatric Endocrinology and Diabetes, St. Christopher’s Hospital for Children, 3601 A Street, Philadelphia, PA 19134, USA, Phone: +1 215 427 8100 (office), Fax: +1 215 427 8105, E-mail: zshoar@gmail.com; zshoar@live.com

References

1. Duncan PA, Shapiro LR, Stangel JJ, Stangel JJ, Klein RM, et al. The MURCS association: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. J Pediatr 1979;95:399–402.10.1016/S0022-3476(79)80514-4Search in Google Scholar

2. Oppelt P, Renner SP, Kellermann A, Brucker S, Hauser GA, et al. Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging. Hum Reprod 2006;21:792–7.10.1093/humrep/dei381Search in Google Scholar PubMed

3. Strubbe EH, Cremers CW, Willemsen WN, Rolland R, Thijn CJ. The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome without and with associated features: two separate entities? Clin Dysmorphol 1994;3:192–9.10.1097/00019605-199407000-00002Search in Google Scholar

4. Sultan C, Biason-Lauber A, Philibert P. Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings. Gynecol Endocrinol 2009;25:8–11.10.1080/09513590802288291Search in Google Scholar PubMed

5. Borges Mde A, Pires ML, Monteiro DL, Santos SR. Atipical form of Mayer-Rokitansky-Kuster-Hauser syndrome with renal malformation and skeletal abnormalities (MURCS association). Rev Bras Ginecol Obstet 2012;34:133–8.Search in Google Scholar

6. Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med 2004;351:792–8.10.1056/NEJMoa040533Search in Google Scholar PubMed

7. Philibert P, Biason-Lauber A, Rouzier R, Pienkowski C, Paris F, et al. Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and müllerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab 2008;93:895–900.10.1210/jc.2007-2023Search in Google Scholar PubMed

8. Philibert P, Biason-Lauber A, Gueorguieva I, Stuckens C, Pienkowski C, et al. Molecular analysis of WNT4 gene in four adolescent girls with mullerian duct abnormality and hyperandrogenism (atypical Mayer-Rokitansky-Küster-Hauser syndrome). Fertil Steril 2011;95:2683–6.10.1016/j.fertnstert.2011.01.152Search in Google Scholar PubMed

9. Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, et al. WNT4 deficiency – a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome. Hum Reprod 2007;22:224–9.10.1093/humrep/del360Search in Google Scholar PubMed

10. Morcel K, Camborieux L. Programme de Recherches sur les Aplasies Müllériennes, Guerrier D. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet J Rare Dis 2007 14;2:13.10.1186/1750-1172-2-13Search in Google Scholar PubMed PubMed Central

11. Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP. Female development in mammals is regulated by Wnt-4 signalling. Nature 1999;397:405–9.10.1038/17068Search in Google Scholar PubMed

12. Acién P, Acién M, Sánchez-Ferrer M. Complex malformations of the female genital tract. New types and revision of classification. Hum Reprod 2004;19:2377–84.10.1093/humrep/deh423Search in Google Scholar PubMed

13. Pizzo A, Laganà AS, Sturlese E, Retto G, Retto A, et al. Mayer-Rokitansky-Kuster-Hauser syndrome: embryology, genetics and clinical and surgical treatment. ISRN Obstet Gynecol 2013;2013:628717.10.1155/2013/628717Search in Google Scholar PubMed PubMed Central

14. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. U.S. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. Available at http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf. Accessed on 12/14/2012.Search in Google Scholar

15. Jameson J, De Groot LJ. Endocrinology adult and pediatrics, 6th edition. Philadelphia, PA: Sunders, 2010:2148–90.Search in Google Scholar

16. Heikkilä M, Peltoketo H, Vainio S. Wnts and the female reproductive system. J Exp Zool 2001;290:616–23.10.1002/jez.1112Search in Google Scholar PubMed

17. Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis – a look outside the nucleus. Science 2000;287:1606–9.10.1126/science.287.5458.1606Search in Google Scholar PubMed

18. Maatouk DM, DiNapoli L, Alvers A, Parker KL, Taketo MM, et al. Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet 2008;17:2949–55.10.1093/hmg/ddn193Search in Google Scholar PubMed PubMed Central

19. Baillet A, Mandon-Pépin B, Veitia R, Cotinot C. Genetics of early ovarian differentiation: recent data. Biol Aujourdhui 2011;205:201–21.10.1051/jbio/2011021Search in Google Scholar PubMed

20. Bernard P, Harley VR. Wnt4 action in gonadal development and sex determination. Int J Biochem Cell Biol 2007;39:31–43.10.1016/j.biocel.2006.06.007Search in Google Scholar PubMed

21. Pellegrino M, Maiorino R, Schonauer S. WNT4 signaling in female gonadal development. Endocr Metab Immune Disord Drug Targets 2010;10:168–74.10.2174/187153010791213074Search in Google Scholar PubMed

22. Clément-Ziza M, Khen N, Gonzales J, Crétolle-Vastel C, Picard JY, et al. Exclusion of WNT4 as a major gene in Rokitansky-Küster-Hauser anomaly. Am J Med Genet A 2005;137:98–9.10.1002/ajmg.a.30833Search in Google Scholar PubMed

23. Ravel C, Lorenzo D, Dessolle L, Mandelbaum J, McElreavey K, et al. Mutational analysis of the WNT gene family in women with Mayer-Rokitansky- Kuster-Hauser syndrome. Fertil Steril 2209;91:1604–7.10.1016/j.fertnstert.2008.12.006Search in Google Scholar PubMed

24. Drummond JB, Reis FM, Boson WL, Silveira LF, Bicalho MA, et al. Molecular analysis of the Wnt4 gene in 6 patients with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril 2008;90:857–9.10.1016/j.fertnstert.2007.07.1319Search in Google Scholar PubMed

25. Chang X, Qin Y, Xu C, Li G, Zhao X, et al. Mutations in WNT4 are not responsible for Müllerian duct abnormalities in Chinese women. Reprod Biomed Online 2012;24:630–3.10.1016/j.rbmo.2012.03.008Search in Google Scholar PubMed

26. Guerrier D, Mouchel T, Pasquier L, Pellerin I. The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina) – phenotypic manifestations and genetic approaches. J Negat Results Biomed 2006;5:1.10.1186/1477-5751-5-1Search in Google Scholar PubMed PubMed Central

27. Heikkilä M, Peltoketo H, Leppäluoto J, Ilves M, Vuolteenaho O, et al. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 2002;143:4358–65.10.1210/en.2002-220275Search in Google Scholar PubMed

28. Church V, Nohno T, Linker C, Marcelle C, Francis-West P. Wnt regulation of chondrocyte differentiation. J Cell Sci 2002;115:4809–18.10.1242/jcs.00152Search in Google Scholar PubMed

29. Alfieri CM, Cheek J, Chakraborty S, Yutzey KE. Wnt signaling in heart valve development and osteogenic gene induction. Dev Biol 2010;338:127–35.10.1016/j.ydbio.2009.11.030Search in Google Scholar PubMed PubMed Central

30. Brisken C, Heineman A, Chavarria T, Elenbaas B, Tan J, et al. Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev 2000;14:650–4.10.1101/gad.14.6.650Search in Google Scholar

31. Murugan S, Shan J, Kühl SJ, Tata A, Pietilä I, et al. WT1 and Sox11 regulate synergistically the promoter of the Wnt4 gene that encodes a critical signal for nephrogenesis. Exp Cell Res 2012;318:1134–45.10.1016/j.yexcr.2012.03.008Search in Google Scholar PubMed

32. Tanigawa S, Wang H, Yang Y, Sharma N, Tarasova N, et al. Wnt4 induces nephronic tubules in metanephric mesenchyme by a non-canonical mechanism. Dev Biol 2011;352:58–69.10.1016/j.ydbio.2011.01.012Search in Google Scholar PubMed PubMed Central

33. He W, Kang YS, Dai C, Liu Y. Blockade of Wnt/β-catenin signaling by paricalcitol ameliorates proteinuria and kidney injury. J Am Soc Nephrol 2011;22:90–103.10.1681/ASN.2009121236Search in Google Scholar PubMed PubMed Central

34. Shan J, Jokela T, Peltoketo H, Vainio S. Generation of an allele to inactivate Wnt4 gene function conditionally in the mouse. Genesis 2009;47:782–8.10.1002/dvg.20566Search in Google Scholar

35. Greene RA, Bloch MJ, Huff DS, Iozzo RV. MURCS association with additional congenital anomalies. Hum Pathol 1986;17: 88–91.10.1016/S0046-8177(86)80160-5Search in Google Scholar

36. Krishnan V, Bryant HU, Macdougald OA, Regulation of bone mass by Wnt signaling. J Clin Invest 2006;116:1202–9.10.1172/JCI28551Search in Google Scholar PubMed PubMed Central

Received: 2013-8-17

Accepted: 2013-10-30

Published Online: 2013-12-19

Published in Print: 2014-5-1

Absence of WNT4 gene mutation in a patient with MURCS association

Abstract

References

Journal and Issue

Articles in the same Issue