TY - JOUR
T1 - De Novo 12;17 translocation upstream of sox9 resulting in 46,xx testicular disorder of sex development
AU - Refai, Osama
AU - Friedman, Andrew
AU - Terry, Lori
AU - Jewett, Tamison
AU - Pearlman, Alexander
AU - Perle, Mary Ann
AU - Ostrer, Harry
PY - 2010/2
Y1 - 2010/2
N2 - 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 64.2-64.6Mb (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 upregulation of the testis-determining SOX9 gene during gonadal development and the phenotype of 46,XX testicular DSD.
AB - 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 64.2-64.6Mb (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 upregulation of the testis-determining SOX9 gene during gonadal development and the phenotype of 46,XX testicular DSD.
KW - 12:17 translocation
KW - 46,xx testicular dsd
KW - Arraycgh analysis
KW - FISH
KW - SOX9
KW - Sex determination
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U2 - 10.1002/ajmg.a.33201
DO - 10.1002/ajmg.a.33201
M3 - Article
C2 - 20082466
AN - SCOPUS:75449089508
SN - 1552-4825
VL - 152
SP - 422
EP - 426
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 2
ER -