title: Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction.
abstract: BACKGROUND
  Deletions of Xq chromosome are reported for a number of familial conditions exhibiting premature ovarian failure (POF) and early menopause (EM).
  
  
  RESULTS
  We describe the inheritance of an interstitial deletion of the long arm of the X chromosome associated with either POF or EM in the same family. Cytogenetic studies and heterozygosity mapping by quantitative fluorescent PCR revealed a 46,X,del(X)(q26.2-q28) karyotype in a POF female, in her EM mother, and also in her aborted fetus with severe cardiopathy. Applying a microsatellite approach, we have narrowed the extension of an identical interstitial deletion located between DXS1187 and DXS1073. These data, in line with other mapped deletions, single out the proximal Xq28 as the region most frequently involved in ovarian failure. We also propose that other factors may influence the phenotypic effect of this alteration. Indeed, skewed X inactivation has been ascertained in EM and POF to be associated with different X haplotypes.
  
  
  CONCLUSIONS
  Our analysis indicates that Xq26.2-q28 deletion is responsible for gonad dysgenesis in a family with EM/POF. The dissimilar deletion penetrance may be due to epigenetic modifications of other X genes that can contribute to human reproduction, highlighting that ovarian failure should be considered as a multifactorial disease.
authors.affiliation: Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR 80131, Napoli, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Fimiani
authors.forename: Carmela
authors.initials: C
authors.lastname: Laperuta
authors.forename: Geppino
authors.initials: G
authors.lastname: Falco
authors.forename: Valerio
authors.initials: V
authors.lastname: Ventruto
authors.forename: Michele
authors.initials: M
authors.lastname: D'Urso
authors.forename: Matilde Valeria
authors.initials: MV
authors.lastname: Ursini
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Miano
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D008594:Menopause, Premature / Q000235:genetics*; D018895:Microsatellite Repeats; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D049951:X Chromosome Inactivation