Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Fertil Steril. 2011 Apr;95(5):1595-600. doi: 10.1016/j.fertnstert.2010.12.052. Epub 2011 Jan 22.
To analyze DNA from women with premature ovarian failure (POF) for genome-wide copy-number variations (CNVs), focusing on novel autosomal microdeletions.
Case-control genetic association study.
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
PATIENT(S): Of 89 POF patients, eight experienced primary amenorrhea and 81 exhibited secondary amenorrhea before age 40 years.
INTERVENTION(S): Genomic DNA from peripheral blood samples was analyzed for CNVs using high-resolution single-nucleotide polymorphism (SNP) arrays.
MAIN OUTCOME MEASURE(S): Identification of novel CNVs in 89 POF cases, using the Database of Genomic Variants as a control population.
RESULT(S): A total of 198 autosomal CNVs were detected by SNP arrays, ranging in size from 0.1 Mb to 3.4 Mb. These CNVs (>0.1 Mb) included 17 novel microduplications and seven novel microdeletions, six of which contained the coding regions 8q24.13, 10p15-p14, 10q23.31, 10q26.3, 15q25.2, and 18q21.32. Most of the novel CNVs were derived from autosomes rather than the X chromosome.
CONCLUSION(S): The present pilot study revealed novel microdeletions/microduplications in women with POF. Two novel microdeletions caused haploinsufficiency for SYCE1 and CPEB1, genes known to cause ovarian failure in knockout mouse models. Chromosomal microarrays may be a useful adjunct to conventional karyotyping when evaluating genomic imbalances in women with POF.
分析患有卵巢早衰（POF）的女性的 DNA，以寻找全基因组拷贝数变异（CNVs），重点关注新的常染色体微缺失。
病例对照遗传关联研究。
德克萨斯州休斯顿贝勒医学院妇产科。
89 名 POF 患者中，8 名患者原发性闭经，81 名患者 40 岁前出现继发性闭经。
使用高分辨率单核苷酸多态性（SNP）芯片分析外周血样本中的基因组 DNA 以检测 CNVs。
使用基因组变异数据库作为对照人群，在 89 例 POF 病例中鉴定新的 CNVs。
SNP 阵列共检测到 198 个常染色体 CNVs，大小从 0.1Mb 到 3.4Mb 不等。这些 CNVs（>0.1Mb）包括 17 个新的微重复和 7 个新的微缺失，其中 6 个包含编码区域 8q24.13、10p15-p14、10q23.31、10q26.3、15q25.2 和 18q21.32。大多数新的 CNVs 来自常染色体而不是 X 染色体。
本初步研究揭示了 POF 女性中的新的微缺失/微重复。两个新的微缺失导致 SYCE1 和 CPEB1 基因的单倍体不足，这些基因在敲除小鼠模型中导致卵巢衰竭。当评估 POF 女性的基因组失衡时，染色体微阵列可能是常规核型分析的有用辅助手段。
