Mixed gonadal dysgenesis in a child with isodicentric Y chromosome: Does the relative proportion of the 45,X line really matter?

Marwan Shinawi, Mark P. Cain, Brian A. VanderBrink, David J. Grignon, Drew Mensing, M. Lance Cooper, Patricia Bader, Sau Wai Cheung

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Isodicentric Y chromosomes [idic(Y)] cause several sex-linked phenotypes ranging from typical Turner syndrome, to phenotypic males, and to those with ambiguous genitalia. The idic(Y) are unstable during mitosis and therefore result in mosaicism with an additional cell line. The associated phenotypic heterogeneity was attributed to variable location of the breakpoints and to the proportion of idic(Y)-containing cells in gonads and other tissues. We report on a phenotypic and cytogenetic characterization of an apparently male patient with ambiguous genitalia and mixed gonadal dysgenesis who was found to be mosaic 45,X/46,X,idic(Y). Unexpectedly, the histologically male gonad showed a predominant proportion of 45,X cells suggesting that additional factors, other than the proportion of the 45,X cell line and the location of the breakpoint, may play a role in gonadal determination and differentiation. Our observation suggests that the timing of the mitotic loss of idic(Y) during gonadal ontogenesis and the proportion of SRY positive pre-Sertoli cells in the gonad are probably more relevant than the postnatal proportion of the different mosaic clones. We discuss the dynamic nature of mitotic instability of isodicentric Y chromosomes and the fundamental role of Sertoli cells in gonadal differentiation and their contribution to the phenotypic variability.

Original languageEnglish (US)
Pages (from-to)1832-1837
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume152
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • Ambiguous genitalia
  • Isodicentric Y chromosome
  • Mixed gonadal dysgenesis
  • Mosaicism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

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