Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction.
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.
Fimiani
Giorgia
G
Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR 80131, Napoli, Italy.
Laperuta
Carmela
C
Falco
Geppino
G
Ventruto
Valerio
V
D'Urso
Michele
M
Ursini
Matilde Valeria
MV
Miano
Maria Giuseppina
MG
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