title: De novo 12;17 translocation upstream of SOX9 resulting in 46,XX testicular disorder of sex development.
abstract: 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.
authors.affiliation: Human Genetics Program, Department of Pediatrics, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Osama
authors.initials: O
authors.lastname: Refai
authors.forename: Andrew
authors.initials: A
authors.lastname: Friedman
authors.forename: Lori
authors.initials: L
authors.lastname: Terry
authors.forename: Tamison
authors.initials: T
authors.lastname: Jewett
authors.forename: Alexander
authors.initials: A
authors.lastname: Pearlman
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Perle
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
mesh_terms: 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
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human