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De novo 12;17 translocation upstream of SOX9 resulting in 46,XX testicular disorder of sex development
Author(s) -
Refai Osama,
Friedman Andrew,
Terry Lori,
Jewett Tamison,
Pearlman Alexander,
Perle Mary Ann,
Ostrer Harry
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33201
Subject(s) - testis determining factor , biology , breakpoint , sox9 , genetics , sex reversal , gonadal dysgenesis , fluorescence in situ hybridization , chromosomal translocation , disorders of sex development , y chromosome , chromosome , pseudogene , comparative genomic hybridization , gene , genome , gene expression , anatomy
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 ≥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. © 2010 Wiley‐Liss, Inc.