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

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. Array comparative genomic hybridization for the detection of submicroscopic copy number variations of the X chromosome in women with premature ovarian failure Sir, 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 Xq13.3-q21.1, Xq26-28 and Xp11.2-22.1; however, the majority of breakpoints within these regions have been mapped to gene-free genomic regions (Prueitt et al., 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. For our study, patients were women with POF consecutively referred to the Department of Obstetrics and Gynaecology in Auck-land; their ages ranged from 15 to 39 years (average 27 years). Ethical approval is previously described (Shelling, 2000). The diagnosis of POF was made following the cessation of menses for 6 months or more before the age of 40 years, coincident with FSH concentrations greater than 40 IU/l. All women with POF were 46, XX with normal FMR1 CGG repeats. Women with an identifiable cause of menopause were excluded. A personal and family history were taken; physical examination by a clinical geneticist excluded features of a syndrome. The X chromosome tiling path array is described elsewhere (Froyen et al., 2007). There were 1875 genomic clones from the X chromosome with a resolution of 80 kb. Data normalization was performed against the median of the spot ratios of all clones. Cy5/Cy3 ratios for each clone were plotted in a log2 scale (Y-axis) relative to the position on the X chromosome (X-axis). Clones with log2 ratios outside the 20.3 –0.3 interval were considered aberrant. A …