Mutational analysis of the WNT gene family in women with Mayer-Rokitansky-Kuster-Hauser syndrome

A novel homozygous missense mutation (c.610G>A, p.Gly204Ser) in the WNT7A gene causes tetra‐amelia in two Saudi families

“…Although asymmetrical chest, rudimentary uterus (V-1, index II), and renal anomaly (V-3, index III) are unique findings and have not yet been described. To our knowledge, previous studies [Timmreck et al, 2003;Ravel et al, 2009] of genitourinary anomalies were not found to be associated with WNT7A mutation. Thus, one of the patients reported here (V-1, index II), appears to represent the first individual with rudimentary uterus associated with a WNT7A mutation.…”

“…Previously, only two homozygous mutations have been described [Woods et al, 2006]; a missense mutation in exon 3 (c.630G>A, which predicts p.Ala109Thr) causing FS, and a mutation in exon 4 (c.1179C>T, which predicts p.Arg292Cys) underlying AA/RRS. However, no WNT7A mutation has been observed in any of the M€ ullerian agenesis cases so far [Timmreck et al, 2003;Ravel et al, 2009].…”

Mullerian dysgenesis: a critical review of the literature

“…Moreover, sequencing of the WNT4 gene in 19 MRKH patients reinforced the notion that Wnt4 mutations leads to an MRKH-like syndrome associated with hyperandrogenism, which might be a distinct clinical and genetic entity from MRKH syndrome [65,67,68]. Additional studies involving mutational analysis of the WNT4 gene in women with MRKH syndrome have reached similar conclusions and exclude WNT4 as a major gene responsible for MRKH without virilization [36,59,67,69].…”

“…58]. To date, no mutation in either Wnt5a or Wnt7a has been reported in women suffering from MRKH syndrome [59,60]. Similarly, although previous studies have demonstrated that Wnt9b plays a primary role in the development of the mammalian kidney and reproductive system [61], an examination of 11 patients with MRKH syndrome failed to identify any mutations in the WNT9b gene [62].…”

Structural Abnormalities of the Female Reproductive Tract

“…WNT4 deficiency has been described in small series of patients with Müllerian duct failure, but crucially these patients also have androgen excess (Biason-Lauber et al 2004 and it has been suggested that this defines WNT4 deficiency as a separate clinical entity to MRKH syndrome (Biason-Lauber et al 2007). More recently a genetic study of 11 members of the same family with MRKH syndrome failed to observe causal mutations in several WNT genes, suggesting that mutations in the coding sequence of these genes are not responsible for MRKH (Ravel et al 2009). …”