Department of Reproductive Medicine and Gynecology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
Fertil Steril. 2011 Apr;95(5):1584-8.e1. doi: 10.1016/j.fertnstert.2011.01.018. Epub 2011 Feb 12.
To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions.
Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome.
Multicenter genetic cohort study in the Netherlands.
PATIENT(S): 108 Dutch Caucasian women with POI, 97 of whom passed quality control, who had a normal karyogram and absent fragile X premutation, and 235 healthy Dutch Caucasian women as controls.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Amount and locus of X chromosomal microdeletions or duplications.
RESULT(S): Intensity differences between SNP probes identify microdeletions and duplications. The initial analysis identified an overrepresentation of deletions in POI patients. Moreover, CNVs in two genes on the Xq21.3 locus (i.e., PCDH11X and TGIF2LX) were statistically significantly associated with the POI phenotype. Mean size of identified CNVs was 262 kb. However, in the validation study the identified putative Xq21.3 deletions samples did not show deviations in intensities in consecutive probes.
CONCLUSION(S): X chromosomal submicroscopic CNVs do not play a major role in Caucasian POI patients. We provide guidelines on how submicroscopic cytogenetic POI research should be conducted.
研究原发性卵巢功能不全（POI）患者是否存在 X 染色体上的亚微观拷贝数变异（CNVs），POI 的定义为 40 岁前自发性继发性闭经，且至少两次促卵泡激素（FSH）水平>40IU/L。
对全基因组 Illumina 370k CNV BeadChips 生成的单核苷酸多态性（SNP）探针强度数据进行分析，然后使用包含 48325 个探针的定制超高密度比较基因组杂交阵列对鉴定出的位点进行验证，这些探针均匀分布在 X 染色体上。
荷兰多中心遗传队列研究。
患者（或样品）：108 名荷兰白种人 POI 患者，其中 97 名通过质量控制，这些患者核型正常，脆性 X 前突变缺失，235 名荷兰白种人健康女性作为对照。
无。
X 染色体微缺失或重复的数量和位置。
SNP 探针之间的强度差异可识别微缺失和重复。初步分析显示 POI 患者中存在缺失的过度表达。此外，Xq21.3 基因座上两个基因（即 PCDH11X 和 TGIF2LX）的 CNVs 与 POI 表型呈统计学显著相关。鉴定出的 CNVs 的平均大小为 262kb。然而，在验证研究中，鉴定出的疑似 Xq21.3 缺失样本在连续探针中并未显示出强度偏差。
X 染色体亚微观 CNVs 并非在白种人 POI 患者中起主要作用。我们提供了如何进行亚微观细胞遗传学 POI 研究的指导方针。
