NOVEL POSTZYGOTIC NONSENSE MUTATION IN SRY IN FAMILIAL XY GONADAL-DYSGENESIS

The Y chromosome gene SRY plays an important role in normal male sexua l development and is thought to be the testis-determining factor. We d escribe a familial nonsense mutation in SRY, shared by two XY sisters with complete gonadal dysgenesis and, in a mosaic manner, by their fat her. This mutation, consisting of a C to T transition in position 1 of codon 97 of SRY,results in a truncated peptide with an incomplete DNA -binding domain. The mutation is also present in the father of the two cases, but a portion of wild-type SRY also remains. Our data suggest that the father suffered a postzygotic mutation early in development, but that he retained a remnant of functional SRY protein that accounts for his normal development.