title: DNA copy number variations in patients with 46,XY disorders of sex development.
abstract: OBJECTIVE
  Less than 50% of cases of 46,XY disorders of sex development are genetically defined after karyotyping and/or sequencing of known causal genes. Since copy number variations are often missed by karyotyping and sequencing, we assessed patients with unexplained 46,XY disorders of sex development using array comparative genomic hybridization for possible disease causing genomic variants.
  
  
  METHODS
  DNA from unexplained cases of 46,XY disorders of sex development were tested by whole genome array comparative genomic hybridization. In cases where novel copy number variations were detected parental testing was performed to identify whether copy number variations were de novo or inherited.
  
  
  RESULTS
  Of the 12 patients who underwent array comparative genomic hybridization testing 2 had possible copy number variations causing disorders of sex development, both maternally inherited microdeletions. One case, with a maternal history of premature ovarian failure, had a cosegregating microdeletion on 9q33.3 involving NR5A1. The other case, with a maternal family history of congenital heart disease, had a cosegregating microdeletion on 8p23.1 upstream of GATA4.
  
  
  CONCLUSIONS
  In this cohort copy number variations involving or adjacent to known causal genes led to 46,XY disorders of sex development in 2 of 12 previously unexplained cases (17%). Copy number variation testing is clinically indicated for unexplained cases of 46,XY disorders of sex development to aid in genetic counseling for family planning.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Harrison
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Candace F
authors.initials: CF
authors.lastname: Granberg
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Melise
authors.initials: M
authors.lastname: Keays
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Martinez
authors.initials: M
authors.lastname: Hill
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Gwen M
authors.initials: GM
authors.lastname: Grimsby
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: linda.baker@childrens.com.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree
keywords: DNA copy number variations; comparative genomic hybridization; disorders of sex development