• PMID: 21048976
• Gene Name: DMRT1
• Condition: Disorders of sexual development (DSD)
• Association: The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candid
• Population size: 9067
• Population details: 9067 (116 with idiopathic DSD, 8951 controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: SRY, DMRT1, FGFR2, KANK1, ADCY2 and ZEB2
• Other associated phenotypes: Disorders of sexual development (DSD)

Identification of de novo copy number variants associated with human disorders of sexual development

Tannour-Louet M, Han S, Corbett ST, Louet JF, Yatsenko S, Meyers L, Shaw CA, Kang SH, Cheung SW, Lamb DJ.

Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2%) evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10(-12)). The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development. FAU - Tannour-Louet, Mounia AU - Tannour-Louet M AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas, United States of America. mlouet@bcm.edu FAU - Han, Shuo AU - Han S FAU - Corbett, Sean T AU - Corbett ST FAU - Louet, Jean-Francois AU - Louet JF FAU - Yatsenko, Svetlana AU - Yatsenko S FAU - Meyers, Lindsay AU - Meyers L FAU - Shaw, Chad A AU - Shaw CA FAU - Kang, Sung-Hae L AU - Kang SH FAU - Cheung, Sau Wai AU - Cheung SW