De novo 12;17 translocation upstream of SOX9 resulting in 46,XX testicular disorder of sex development.
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.
Refai
Osama
O
Human Genetics Program, Department of Pediatrics, New York University School of Medicine, New York, New York 10016, USA.
Friedman
Andrew
A
Terry
Lori
L
Jewett
Tamison
T
Pearlman
Alexander
A
Perle
Mary Ann
MA
Ostrer
Harry
H
D002881:Chromosomes, Human, Pair 12; D002886:Chromosomes, Human, Pair 17; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D055758:SOX9 Transcription Factor / Q000235:genetics*; D019849:Sex Determination Processes; D046468:Sexual Development / Q000235:genetics; D016615:Telomere / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism; D014178:Translocation, Genetic
D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human