Array comparative genomic hybridization for the detection of submicroscopic copy number variations of the X chromosome in women with premature ovarian failure.

摘要

Comments of Dr Kvaskoff et at. are all of utmost interest and value. Some of the limits of our study were already mentioned in our original paper, but they are clarified in this letter better. Overall, we thus just thank the authors for their precious and constructive comments. Evidence suggests that structural integrity of the X chromosome is important in the maintenance of ovarian function. Breakpoints of X chromosome rearrangements defined three critical regions for ovarian function between Xql3.3-q2l .1, Xq26-28 and Xp I 1.2-22.1; however, the majority of breakpoints within these regions have been mapped to gene-free genomic regions (Prueitt et a/., 2002). One hypothesis is that chromosome dynamics on the X chromosome could be sensitive to structural changes, interfering with normal chromosome pairing during meiosis, leading to accelerated oocyte apoptosis (Burgoyne and Baker, 1984). A publication by Quilter et al. (2010), reported 15 novel copy number variations (CNVs) on the X chromosome in 20/42 (48%) of women with premature ovarian failure (POF). We have generated similar results that support the hypothesis that cryptic submicro-scopic CNVs of the X chromosome may be associated with POF; however, our detection rate of two novel CNVs in 2/50 (4%) of women with POF using a similar resolution X chromosome tiling pathway was lower.