Molecular analysis of the β-catenin gene in patients with the Mayer-Rokitansky-Küster-Hauser syndrome

Abstract

Purpose To study the β-catenin gene in a group of MayerRokitansky-Küster-Hauser patients. Methods Twelve patients with the Mayer-RokitanskyKüster-Hauser syndrome were included in this study. DNA was extracted from peripheral blood and the region codifying β-catenin GSK-3β phosphorylation sites on exon 3 was amplified. PCR products were purified and directly sequenced.Results No mutations were found in the GSK-3β phosphorylation sites on exon 3 of β-catenin gene in this group of patients with the MRKH syndrome. Conclusions β-catenin gene mutations are an unlikely cause of the MRKH syndrome.Keywords Mayer-Rokitansky-Küster-Hauser syndrome . β-catenin . molecular analysis . Müllerian ducts . anti-Müllerian hormone Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (MIM *277000), a congenital malformation of the Müllerian ducts, is the second most common cause of primary amenorrhea, occurring in one in every 4,000 to 5,000 female live births. The extent of MRKH anomaly is variable, ranging from upper vaginal atresia and rudimentary uterus to total uterine, fallopian tubes and upper vaginal agenesis. Additional congenital skeletal and renal abnormalities are present in approximately 30% of the patients [1]. Clinically, the diagnosis should be suspected if primary amenorrhea and infertility are present in 46, XX individuals with normal ovaries and normal secondary sexual characteristics.The cause of the MRKH syndrome remains unexplained. The presence of familial clustering described in previous studies suggests a genetic defect [2,3]. Nevertheless, the molecular basis of the MRKH syndrome has not yet been established. The putative defective gene could be either involved in the process of Müllerian duct formation, or associated with abnormal activation of the anti-Müllerian hormone (AMH) signaling pathway, leading to Müllerian duct regression. Indeed, both hypotheses could ultimately result in the MRKH syndrome phenotype.Comprising the first group, several genes encoding transcription factors and signaling molecules have been studied. WT1, PAX-2, WNT-7a, RXR-alpha, RXR-gamma, HOXA-7 to HOXA-13, and PBX-1 are genes required for Müllerian duct formation and differentiation, which have been evaluated in different groups of patients and were all excluded as causes of the MRKH syndrome [4][5][6][7][8]. Analysis of WNT4, a gene encoding a signaling molecule crucial for ovarian and uterine development, has provided us with interesting information. WNT4 gene mutations have been described in patients with Mullerian duct abnormalities and hyperandrogenism [9-11], but were not found in patients with the classic MRKH syndrome phenotype [6,[11][12][13]. These results suggest that WNT4 gene mutation is a clinical phenotype distinct from the isolated MRKH, and exclude it J Assist Reprod Genet (2008) 25:511-514 DOI 10.1007/s10815-008-9261-y Capsule β-catenin gene mutations were not detected in a group of twelve patients with the Mayer-Rokitansky Küster-Hauser (MRKH) anomaly.

SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome

“…This disorder is characterized by malformations of the structures derived from the müllerian ducts. 10,13,15 Investigated loci include antimüllerian hormone and its receptor CTNNB1 18,19 and genes involved in early development such as WT1, 20 PAX2, 20 HOX, 21,22 LMX1, and TCF2. 1 MRKH syndrome may occur as an isolated abnormality (MRKH type 1 syndrome).…”

Analysis of WNT9B mutations in Chinese women with Mayer–Rokitansky–Küster–Hauser syndrome

“…2005; Drummond et al, 2008a;Drummond et al, 2008b;Lalwani et al, 2008;Liatsikos et al, 2010;Oppelt et al, 2005;Ravel et al, 2009Ravel et al, , 2012Zenteno et al, 2004). However, these studies did not reveal plausible causative mutations.…”

MURCS association with situs inversus totalis: Expanding the spectrum or a novel disorder

“…Mutations in CFTR (cystic fibrosis transmembrane conductance regulator) gene were studied in a cohort of congenital absence of uterus and vagina, in a case control setting, no significance was found in the mutations between controls and patients [16]. Molecular analyses to look for mutations in the glycogen synthetase kinase 1 (GSK1) phosphorylation site in the exon 3 of beta catenin gene, which is the downstream effector of Wnt pathway-yielded, no results in association with MRKH syndrome [17]. Non-overlapping partial duplication of chromosome Xpter were observed in 5/30 patients in a cohort, out of which two were familial.…”