Role for anti-M�llerian hormone in congenital absence of the uterus and vagina

Abstract

Molecular genetic techniques were used to determine if mutations in the genes encoding anti-Müllerian hormone (AMH) (also known as Müllerian inhibiting substance (MIS)) and its receptor (AMHR) are commonly present in patients with congenital absence of the uterus and vagina (CAUV). Twenty-two CAUV patients and 96 control subjects from diverse ethnic groups were studied after obtaining informed consent. Genomic DNA samples prepared from leukocytes were digested separately with several different restriction enzymes, and the resultant fragments were analyzed for restriction fragment melting polymorphisms (RFMPs) by denaturing gradient gel electrophoresis (DGGE). Electrophoretic mobility of DNA fragments which were 200-700 base pairs in length was compared using polyacrylamide gels that included linear gradients of denaturing solvents designed to separate DNA fragments according to sequence-dependent variation in thermal stability. Two RFMPs were found in the AMH gene in both patients and normal control subjects. One RFMP in the AMHR gene was present at low frequencies in both patients and normal control subjects. No RFMPs specific to CAUV patients were found in either gene. Because no mutations or rare DNA sequence polymorphisms were detected in the AMH and the AMHR genes in this group of CAUV patients, it is unlikely that either gene commonly has an etiologic role in CAUV.

Molecular analysis of the WNT4 gene in 6 patients with Mayer-Rokitansky-Küster-Hauser syndrome

“…In this search several genes have been studied, including transcription factors and signaling molecules, but the results have been consistently negative (9,(12)(13)(14)(15)(16)(17)(18). The reports of the association of the MRKH defect with other genetic syndromes, such as Klippel-Feil syndrome (MIM no.…”

Associations of Polymorphisms in WNT9B and PBX1 with Mayer-Rokitansky-Küster-Hauser Syndrome in Chinese Han

“…AMH signal transduction induces the degradation of MDs, and has been long implicated in MRKH syndrome. Previous studies have screened the entire AMH gene and its receptor for DNA sequence variations and have measured this hormone levels in MRKH syndrome patients, reporting negative results [14, 33, 34]. The associated mutation c.934C>T, particularly the homozygous mutation (TT), was predicted to interfere with the normal functioning of the AMH protein and to disturb AMH-dependent Müllerian degeneration.…”

Le syndrome de Mayer-Rokitansky-Küster-Hauser (MRKH) : clinique et génétique

“…Cette théorie fut ensuite rejetée devant les résul-tats contradictoires d'une étude portant sur 22 patientes MRKH [75]. En effet, dans cette étude, aucune mutation du gène de l'AMH et de son récepteur n'a été retrouvée chez ces femmes.…”