Persistence of Müllerian derivatives in males.

The persistent müllerian duct syndrome is a rare, autosomal recessive disorder, characterized by the persistence of müllerian duct derivatives-uterus and fallopian tubes-in genetic males otherwise normally virilized. We have collected DNA from 69 families with this syndrome. In 45%, a mutation of the anti-müllerian hormone (AMH) gene was detected; 52% were homozygous. The level of circulating AMH was extremely low in the great majority of patients, even before puberty, when AMH levels are normally high. Single-strand conformation polymorphism (SSCP)-polymerase chain reaction (PCR) was a very effective screening method. In 39% of families, characterized by an AMH level normal for the age of the patient, a mutation of the type II receptor of AMH was detected by automatic sequencing, because SSCP-PCR was not very effective. Forty-eight percent of the mutations were homozygous. A 27-base-pair deletion in exon 10 was noted in 45% of the families. When this very common mutation is not taken into account, the proportion of recurrent mutations is 42% for the AMH gene and 33% for the AMH receptor type II gene. In 16% of families, no mutation of either the AMH or the AMH receptor gene was detectable; this group may correspond to mutations of unknown genes involved in AMH processing or in downstream AMH transduction. Copyright 2000 Wiley-Liss, Inc.