The Y-chromosomal and autosomal testis-determining genes

Abstract

It has been conclusively shown that a majority of XX males has acquired Y-chromosome-specific DNA (Y-DNA) sequences from their father’s Y chromosome. Testicular differentiation in these XX males is very likely induced by the testis-determining factor, TDF, normally located on Yp. The phenotypic expression of TDF in the presence of two X chromosomes is a male habitus, dysgenetic scrotal testes and no ambiguity of the genitalia. Among those XX males who do not have Y-DNA detectable by presently used methods, some, but not all have ambiguity of the genitalia with or without hypospadias. XX true hermaphrodites are characterized by the presence of both testicular and ovarian tissue and have ambiguous genitalia. They do not have Y-DNA. Several instances of familial XX maleness are critically analysed. In these pedigrees, most of the affected individuals are true hermaphrodites or XX males with ambiguous genitalia; in at least one family no Y-DNA occurred in these individuals. Typical autosomal dominant inheritance of XX testicular differentiation occurs in informative pedigrees. The suggested conclusion is that an autosomal dominant testis-determining factor, TDFA, exists. TDFA shows somewhat variable expression in XX individuals often causing genital ambiguity or true hermaphrodism. TDFA has no phenotypic effect on XY individuals. It is argued that XX males without presently detectable Y-DNA are caused either by TDF or TDFA.