WNT9B in 542 Chinese women with Müllerian duct abnormalities: mutation analysis

Abstract

The WNT9B gene is a common organizing signal regulating different segments of the mammalian urogenital system and plays a primary role in the development of the female reproductive tract. The aim of the present work was to examine the presence of WNT mutations in a population of women with Müllerian duct abnormalities (MDA) in order to elucidate whether mutations in WNT9B are causative for MDA in Chinese women. Initially, 191 Chinese MDA patients and 192 healthy individuals (controls) were recruited. All coding regions were amplified by PCR and sequenced to search for variants. To verify the initial results, the numbers of patients and ethnic-matched controls were expanded to 542 and 563, respectively. One known single-nucleotide polymorphism and four novel variants were identified in the first stage: two were synonymous; the other two were rare nonsynonymous novel variants (c.566G>A (p.Arg189Gln) and c.773G>A (p.Arg258His)). None of the four novel variants was found in controls. In the second stage, both novel nonsynonymous variants were detected in MDA cases and controls. The results indicate that mutations in the coding sequence of WNT9B are not responsible for MDA in the Chinese population.

Mutations in WNT9B are associated with Mayer–Rokitansky–Küster–Hauser syndrome

“…However, it is unclear whether the mutations were found in trans or in cis. Tang et al (2014) found the two novel WNT9B variants c.566G>A (p.Arg189Gln) and This patient additionally has a likely pathogenic missense mutation in TBX6.…”

“…However, it is unclear whether the mutations were found in trans or in cis . Tang et al (2014) found the two novel WNT9B variants c.566G>A (p.Arg189Gln) and c.773G>A (p.Arg258His) in a first stage analysis of 191 Chinese women with MD anomalies . In a second stage analysis, 351 additional cases and 563 controls were screened for the presence of these two WNT9B variants.…”

“…c.773G>A (p.Arg258His) in a first stage analysis of 191 Chinese women with MD anomalies (12). In a second stage analysis, 351 additional cases and 563 controls were screened for the presence of these two WNT9B variants.…”

“…In this context, two novel WNT9B mutations have been reported in a Chinese woman with MRKHS, previously (11). However, another study in the Chinese population found no association between MD anomalies and mutations in WNT9B (12). To investigate whether mutations in WNT9B are causative for MD anomalies in the Caucasian population, we now performed retrospective sequence analyses of WNT9B in our study group.…”

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females

“…Apart from the known reasons such as environmental factors, harmful hormones, ionizing radiation, and drug effects, genetic factors may act as the major cause of MDA [4][5][6]. In the recent two decades, a lot of essential candidate genes related to the development of the mullerian duct have been studied, such as the WNT and HOX families, LHX1, and TBX6 [7][8][9][10][11][12][13][14]. However, most of the researches failed to explain the relationship between the genes and MDA.…”