Role for anti-Mullerian hormone in congenital absence of the uterus and vagina

Molecular genetic techniques were used to determine if mutations in the gen es encoding anti-Mullerian hormone (AMH) (also known as Mullerian inhibitin g substance (MIS)) and its receptor (AMHR) are commonly present in patients with congenital absence of the uterus and vagina (CAW). Twenty-two CAW pat ients and 96 control subjects from diverse ethnic groups were studied after obtaining informed consent. Genomic DNA samples prepared from leukocytes w ere digested separately with several different restriction enzymes, and the resultant fragments were analyzed for restriction fragment melting polymor phisms (RFMPs) by denaturing gradient gel electrophoresis (DGGE). Electroph oretic mobility of DNA fragments which were 200-700 base pairs in length wa s compared using polyacrylamide gels that included linear gradients of dena turing solvents designed to separate DNA fragments according to sequence-de pendent variation in thermal stability. Two RFMPs were found in the AMH gen e in both patients and normal control subjects. One RFMP in the AMHR gene w as present at low frequencies in both patients and normal control subjects. No RFMPs specific to CAW patients were found in either gene. Because no mu tations 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. (C) 2001 Wiley-Liss, Inc.