Clinical and molecular studies in four patients with SRY-positive 46,XX testicular disorders of sex development: implications for variable sex development and genomic rearrangements

J Hum Genet. 2014 Oct;59(10):549-53. doi: 10.1038/jhg.2014.70. Epub 2014 Aug 7.

Abstract

We report four patients with SRY-positive 46,XX testicular disorders of sex development (46,XX-TDSD) (cases 1-4). Case 1 exhibited underdeveloped external genitalia with hypospadias, case 2 manifested micropenis and cases 3 and 4 showed normal external genitalia. The Xp;Yp translocations occurred between the X- and the Y-differential regions in case 1, between PRKX and inverted PRKY in case 2 and between the X-chromosomal short arm pseudoautosomal region and the Y-differential regions in cases 3 and 4. The distance of the Yp breakpoint from SRY was ~0.75 Mb in case 1, ~6.5 Mb in case 2, ~2.3 Mb in case 3 and ~72 kb in case 4. The Xp;Yp translocation occurred within an 87-bp homologous segment of PRKX and PRKY in case 2, and between non-homologous regions with addition of an 18-bp sequence of unknown origin in case 4. X-inactivation analysis revealed random inactivation in cases 1-4. The results argue against the notion that undermasculinization in 46,XX-TDSD is prone to occur when translocated Yp materials are small (<100 kb of the Y-differential region), and imply that the Xp;Yp translocations result from several mechanisms including non-allelic homologous recombination and non-homologous end joining.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 46, XX Testicular Disorders of Sex Development / genetics*
  • Adult
  • Child, Preschool
  • Chromosomes, Human, X*
  • Chromosomes, Human, Y*
  • Comparative Genomic Hybridization
  • DNA End-Joining Repair
  • Female
  • Genes, sry*
  • Homologous Recombination
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Pregnancy
  • Translocation, Genetic*
  • X Chromosome Inactivation
  • Young Adult