Mutations of the AMH Type II Receptor in Two Extended Families with Persistent Mullerian Duct Syndrome: Lack of Phenotype/Genotype Correlation

Our goal was to compare phenotype and genotype in two extended Middle-Eastern families affected by persistent Mullerian duct syndrome due to mutations of the type II anti-Mullerian hormone receptor (AMHR-II). The first, consanguineous, family consisted of 6 boys and 2 girls, the second consisted of 4 girls and 2 boys. In family I, 4 boys and 1 girl were homozygous for a stop mutation in the 9th exon of AMHR-II, removing part of the intracellular domain of the protein. In family II, 1 girl and 1 boy were homozygous for a transversion changing conserved histidine 254 into a glutamine. Both homozygous girls were normal. In the homozygous males, the degree of development of Mullerian derivatives was variable. The uterus was well developed in 2 boys of family I and in the patient from family II; however, in 1 subject from family I, Mullerian derivatives were undetectable. Taken together, the diversity of clinical symptoms within the same sibship and the lack of correlation between the development of the Mullerian derivatives and the severity of the molecular defects suggest highly variable penetrance of the abnormal alleles and/or the existence of other genetic or epigenetic modifiers of gene expression. Copyright (C) 2012 S. Karger AG, Basel