Premium
Mutations in WNT9B are associated with Mayer–Rokitansky–Küster–Hauser syndrome
Author(s) -
Waschk D.E.J.,
Tewes A.C.,
Römer T.,
Hucke J.,
Kapczuk K.,
Schippert C.,
Hillemanns P.,
Wieacker P.,
Ledig S.
Publication year - 2016
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12701
Subject(s) - missense mutation , mayer rokitansky kuster hauser syndrome , mutation , phenotype , nonsense mutation , genetics , gene , mutation testing , medicine , vagina , biology
Mayer–Rokitansky–Küster–Hauser syndrome ( MRKHS ) is a well‐known malformation pattern of the Müllerian ducts ( MDs ) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b‐/‐ mice show a MRKHS ‐like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs , including 109 patients with MRKHS , as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B . Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6 . We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.