title: Submicroscopic copy-number variations associated with 46,XY disorders of sex development.
abstract: BACKGROUND
  Mutations in known causative genes and cytogenetically detectable chromosomal rearrangements account for a fraction of cases with 46,XY disorders of sex development (DSD). Recent advances in molecular cytogenetic technologies, including array-based comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA), have enabled the identification of copy-number variations (CNVs) in individuals with apparently normal karyotypes.
  
  
  RESULTS
  This review paper summarizes the results of 15 recent studies, in which aCGH or MLPA were used to identify CNVs. Several submicroscopic CNVs have been detected in patients with 46,XY DSD. These CNVs included deletions involving known causative genes such as DMRT1 or NR5A1, duplications involving NR0B1, deletions involving putative cis-regulatory elements of SOX9, and various deletions and duplications of unknown pathogenicity.
  
  
  CONCLUSIONS
  The results of recent studies highlight the significance of submicroscopic CNVs as the genetic basis of 46,XY DSD. Molecular cytogenetic analyses should be included in the diagnostic workup of patients with 46,XY DSD of unknown origin. Further studies using aCGH will serve to clarify novel causes of this condition.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan. k-masafumi@mri.biglobe.ne.jp.|Department of Urology, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, 060-8638, Japan. k-masafumi@mri.biglobe.ne.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kon
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan. fukami-m@ncchd.go.jp.
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
keywords: Comparative genomic hybridization; Copy-number variations; Disorders of sex development; Multiplex ligation-dependent probe amplification