Linkage analysis of a kindred with inherited 46,XY partial gonadal dysgenesis

We have reported a kindred in which 46,XY gonadal dysgenesis was inherited in an X-linked (or autosomal dominant sex-limited) manner and in which affected subjects did not have a large duplication of the short arm of the X-chromosome. In the present study we used linkage and sequence analyses to test the role of X-linked and various autosomal genes in the etiology of the familial 46,XY partial gonadal dysgenesis. For analysis of X-linkage, 28 microsatellite polymorphisms and 1 restriction fragment length polymorphism were studied. The genotypes of informative family members were determined at each locus, and data were analyzed. Despite the large number of loci tested, our studies did not establish linkage between the trait and an X-chromosomal locus. With respect to the study of autosomal genes, linkage analysis using a polymorphism within the 3'-untranslated region of the WT1 gene excluded involvement of WT-1 in the etiology of the abnormal gonadal differentiation of the family in this study. Similarly, linkage analysis using four microsatellites on the distal short arm of chromosome 9 was not consistent with linkage. Linkage analysis of a locus close to the SOX9 gene as well as analysis of the coding region of the SOX9 gene suggested that this gene was not associated with the trait in the affected subjects we studied. Our data suggest the role of an autosomal gene in the abnormal gonadal differentiation in the family in the study, but do not formally exclude the role of an X-chromosome gene.