AUTOSOMAL SEX REVERSAL AND CAMPOMELIC DYSPLASIA ARE CAUSED BY MUTATIONS IN AND AROUND THE SRY-RELATED GENE SOX9

A human autosomal XY sex reversal locus, SRA1, associated with the ske letal malformation syndrome campomelic dysplasia (CMPD1), has been pla ced at distal 17q, The SOX9 gene, a positional candidate from the chro mosomal location and expression pattern reported for mouse Sox9, was i solated and characterized, SOX9 encodes a putative transcription facto r structurally related to the testis-determining factor SRY and is exp ressed in many adult tissues, and in fetal testis and skeletal tissue, Inactivating mutations on one SOX9 allele identified in nontranslocat ion CMPD1-SRA1 cases point to haploinsufficiency far SOX9 as the cause for both campomelic dysplasia and autosomal XY sex reversal. The 17q breakpoints in three CMPD1 translocation cases map 50 kb or more from SOX9.