Prenatal Diagnosis of Osteopathia Striata with Cranial Sclerosis in a Male Fetus with a ~330kb Deletion of Xq11.1 Involving the WTX Gene

Patrick L. Wilson^1, , Ashley Davis², Jean Ricci Goodman^{1, 3}, Lauren Notley¹, Shibo Li², Ji-Yun Lee^{2, 4}, Zhongxin Yu⁵, Klaas J. Wierenga² and Andrew F. Wagner¹

¹Department of Obstetrics and Gynecology, Maternal/Fetal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA

²Department of Pediatrics, Genetics Section, University of Oklahoma Health Sciences Center, Oklahoma City, USA

³Deparment of Obstetrics and Gynecology, Maternal/Fetal Medicine, Loyola University, Stritch School of Medicine, Chicago, USA

⁴Department of Pathology, Korea University, Seoul, Korea

⁵Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA

Cite this paper

Patrick L. Wilson, Ashley Davis, Jean Ricci Goodman, Lauren Notley, Shibo Li, Ji-Yun Lee, Zhongxin Yu, Klaas J. Wierenga and Andrew F. Wagner. Prenatal Diagnosis of Osteopathia Striata with Cranial Sclerosis in a Male Fetus with a ~330kb Deletion of Xq11.1 Involving the WTX Gene. American Journal of Medical and Biological Research. 2013; 1(1):33-36. doi: 10.12691/AJMBR-1-1-6

Abstract

Osteopathia striata with cranial sclerosis (OSCS) is a rare X-linked dominant genetic disorder resulting mutation in the WTX gene. Clinically, OSCS presents with linear striations in the metaphyseal region of the long bones and pelvis in combination with sclerosis of the cranium and face. A twenty-seven year old G5T1P3A0L2 woman with a history of peri- and neonatal infant male deaths was referred to us at 22 weeks, 6 days into her recent pregnancy. Ultrasound evaluation identified a male fetus, bilaterally enlarged lateral ventricles, a cloverleaf skull, suspected bilateral cleft lip, nuchal thickening, bilateral bowed radii and ulnae, gastroschisis with herniated viscera, bilateral absent fibula and clubfeet. The results of prenatal testing identified a male fetus with a 330kb Xq11.1 deletion involving the entire WTX gene. Initial microarray analysis of maternal blood identified a normal female karyotype, 46,XX. FISH analysis with a BAC clone mapped to the WTX gene identified low-level mosaicism in blood and buccal samples, 17% and 15%, respectively, which explained the negative maternal microarray result.

Keywords

Osteopathia striata with cranial sclerosis (OSCS), Wilms tumor on the X-chromosome (WTX) gene, Microarray, Mosaic, Osteopetrosis, Germline mosaicism

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References

[1]	Jenkins, Z.A., van Kogelenberg, M., Morgan, T., Jeffs, A., Fukuzawa, R., Pearl, E., Thaller, C., Hing, A.V., Porteous, M.E., Garcia-Miñaur, S., Bohring, A., Lacombe, D., Stewart, F., Fiskerstrand, T., Bindoff, L., Berland, S., Adès, L.C., Tchan, M., David, A., Wilson, L.C., Hennekam, R.C., Donnai, D., Mansour, S., Cormier-Daire, V., and Robertson, S.P, “Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis,” Nature Genetics, 41 (1). 95-100. Jan. 2009.
[2]	Holman, S.K., Daniel, P., Jenkins, Z.A., Herron, R.L., Morgan, T,, Savarirayan, R., Chow, C.W,, Bohring, A., Mosel, A., Lacombe, D., Steiner, B., Schmitt-Mechelke, T., Schroter, B., Raas-Rothschild, A., Miñaur, S.G., Porteous, M., Parker, M., Quarrell, O., Tapon, D., Cormier-Daire, V., Mansour, S., Nash R, Bindoff LA, Fiskerstrand T, and Robertson, S, “The male phenotype in osteopathia striata congenita with cranial sclerosis,”American Journal of Medical Genetics A, 155A (10). 2397-408. Oct. 2011.
[3]	Moisan, A., Rivera, M.N., Lotinun, S., Akhavanfard, S., Coffman, E.J., Cook, E.B., Stoykova, S., Mukherjee, S., Schoonmaker, J.A., Burger, A., Kim, W.J., Kronenberg, H.M., Baron, R., Haber, D.A., and Bardeesy, N, “The WTX tumor suppressor regulates mesenchymal progenitor cell fate specification,” Developmental Cell, 20 (5). 583-96. May 2011.
[4]	Perdu, B., de Freitas, F., Frints, S.G., Schouten, M., Schrander-Stumpel, C., Barbosa, M., Pinto-Basto, J., Reis-Lima, M., de Vernejoul, M.C., Becker, K., Freckmann, M.L., Keymolen, K., Haan, E., Savarirayan, R., Koenig, R., Zabel, B., Vanhoenacker, F.M., and Van Hul, W, “Osteopathia striata with cranial sclerosis due to WTX gene defect,” Journal of Bone and Mineral Research, 25 (1). 82-90. Jan.2010.
[5]	Perdu, B., Lakeman, P., Mortier, G., Koenig, R.., Lachmeijer, A., and Van Hul, W, “Two novel WTX mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis,” Clinical Genetics, 80 (4). 383–8. Oct. 2011.
[6]	Huff, V, “Wilms’ tumours: about tumour suppressor genes, an oncogene, and chameleon gene,” Nature Reviews, Cancer, 11 (2). 111-21. Feb. 2011.
[7]	Chénier, S., Noor, A., Dupuis, L., Stravropoulos, D.J., Mendoza-Londona R. “Osteopathia striata with cranial sclerosis and developmental delay in a male with a mosaic deletion in chromosome region Xq11.2,” American Journal of Medical Genetics, Part A, 158A (11). 2946-52. Nov. 2012.
[8]	Horn, D., Delaunoy, J-P., and Kunze, J, “Prenatal diagnosis of Coffin-Lowry syndrome demonstrates germinal mosaicism confirmed by mutation analysis,” Prenatal Diagnosis, 21 (10). 881-4. Oct. 2001
[9]	Pilozzi-Edmonds, L., Maher, T., Basran, R., Milunsky, A., Al-Thihli, K., Braverman, N., and Alafares, A, “Fraternal twins with Aarskog-Scott syndrome due to maternal germline mosaicism,” American Journal of Med Genetics Part A. 155A (8). 1987-90. Aug. 2011
[10]	Van der Meulen, M.A., van der Meulen, M.J., and te Meermen, G.J, “Recurrence risk for germinal mosaics revisited,” Journal of Medical Genetics, 32 (2). 102-4. Feb. 1995.