Individuals with rare cytogenetic variants have contributed to our understanding of the genetics of sex development and its disorders. Here, we report on a child with a de novo 12;17 translocation, 46,XX,t(12;17)(q14.3;q24.3) chromosome complement, resulting in SRY-negative 46,XX testicular disorder of sex development (46,XX DSD without campomelic dysplasia). The chromosome 12 breakpoint was mapped via array comparative genomic hybridization (aCGH) of a hybrid somatic cell line to 64.2-64.6 Mb (from the p arm telomere). The chromosome 17 breakpoint was mapped to 66.4-67.1 Mb, that is, upstream of SOX9. The location of the chromosome 17 breakpoint was refined by fluorescence in situ hybridization (FISH) at > or =776 kb upstream of SOX9. Thus, the 12;17 translocation removed part of the SOX9 cis-regulatory region and replaced it with a regulatory element from pseudogene LOC204010 or the next gene, Deynar, of chromosome 12, potentially causing up-regulation of the testis-determining SOX9 gene during gonadal development and the phenotype of 46,XX testicular DSD.
Copyright 2010 Wiley-Liss, Inc.