Molecular definition of Xq common-deleted region in patients affected by premature ovarian failure

High-resolution cytogenetic analysis of a large number of women with premat ure ovarian failure (POF) identified six patients carrying different Xq chr omosome rearrangements. The patients (one familial and five sporadic cases) were negative for Turner's stigmata and experienced a variable onset of me nopause. Microsatellite analysis and fluorescent in situ hybridization (FIS H) were used to define the origin and precise extension of the Xq anomalies . All of the patients had a Xq chromosome deletion as the common chromosoma l abnormality, which was the only event in three cases and was associated w ith partial Xp or 9p trisomies in the remaining three. Two of the Xq chromo some deletions were terminal with breakpoints at Xq26.2 and Xq21.2, and one interstitial with breakpoints at Xq23 and Xq28. In all three cases, the de l(X)s retained Xp and Xq specific telomeric sequences. One patient carries a psu dic(Xi with the deletion at Xq22.2 or Xq22.3; the other two [carrying (X:X) and (X;9) unbalanced translocations, respectively] showed terminal d eletions with the breakpoint at Xq22 within the DIAPH2 gene. Furthermore, t he rearranged)X chromosomes were almost totally inactivated, and the extent of the Xq deletions did not correlate with the timing of POF. In agreement with previous results, these findings suggest that the deletion of a restr icted Xq region may be responsible for the POF phenotype. Our analysis indi cates that this region extends from approximately Xq26.2 (between markers D XS8074 and HIGMI) to Xq28 (between markers DXS1113 and ALD) and covers appr oximately 22 Mb of DNA. These data may provide a starting point for the ide ntification of the gene(s) responsible for ovarian development and follicul ogenesis.