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

Abstract

High-resolution cytogenetic analysis of a large number of women with premature ovarian failure (POF) identified six patients carrying different Xq chromosome rearrangements. The patients (one familial and five sporadic cases) were negative for Turner's stigmata and experienced a variable onset of menopause. Microsatellite analysis and fluorescent in situ hybridization (FISH) 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 chromosomal abnormality, which was the only event in three cases and was associated with partial Xp or 9p trisomies in the remaining three. Two of the Xq chromosome 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 del(X)s retained Xp and Xq specific telomeric sequences. One patient carries a psu dic(X) with the deletion at Xq22.2 or Xq22.3; the other two [carrying (X;X) and (X;9) unbalanced translocations, respectively] showed terminal deletions with the breakpoint at Xq22 within the DIAPH2 gene. Furthermore, the 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 restricted Xq region may be responsible for the POF phenotype. Our analysis indicates that this region extends from approximately Xq26.2 (between markers DXS8074 and HIGMI) to Xq28 (between markers DXS 1113 and ALD) and covers approximately 22 Mb of DNA. These data may provide a starting point for the identification of the gene(s) responsible for ovarian development and folliculogenesis.

Microarray detection of a de novo der(X)t(X;11)(q28;p13) in a girl with premature ovarian failure and features of Beckwith–Wiedemann syndrome

“…Results from the investigation of X-autosome balanced translocations and Xq terminal deletions suggest the presence of two loci on Xq (POF1, located at Xq26-q28; and POF2, located at Xq13.3-q22) that appear to be involved in ovarian function (Marozzi et al 2000). Microarray analysis for our patient demonstrated a loss of DNA copy number at the Xq subtelomeric region (Xq28), consistent with the POF1 critical region.…”

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

“…Previous reports have suggested different critical region on Xq arm to be associated with premature ovarian failure (POF) which involve Xq13.3-q22 [29] and Xq26-q28 [41]. Subsequent studies also suggested Xq26.2-q28 [21], Xq27.2/Xq27.3-Xq28 [8] and Xq13-21 and Xq23-28 [44] are the regions associated with POF (Fig. 4).…”

Characterization of a prenatally diagnosed de novo der(X)t(X;Y)(q27;q11.23) of fetus

“…POF1 (Xq23q27 or Xq2628) region deletions are much more commonly related to POF, and the haploinsufficiency of those deleted genes that normally escape X inactivation may be harmful to ovarian function [9]. Marozzi et al [10] studied six POF patients with rearranged Xq chromosomes and revealed that the POF1 region extends from Xq26.2 to Xq28.…”