Abstract: To investigate genetic causes in Chinese women with primary ovarian insufficiency (POI) for genome-wide copy number variations (CNVs), focusing on novel autosomal microdeletions and microduplications. Methods: Genome-wide CNVs analysis using Affymetrix SNP 6.0 array was carried out in 30 Chinese POI subjects. And quantitative PCR (qPCR) was further performed for selected coding regions with microdeletions and microduplications in 30 POI subjects and another 40 POI cases. Results: A total of 101 CNVs were identified by SNP arrays, ranging in size from 0.1 MB to 5.6 MB. These CNVs included 8 novel microduplications and 12 novel microdeletions. Then 4 microdeletions identified in chromosomal regions (10q26.12, 10q26.3, 2p16.3, and 6p26) and 2 microduplications which contained the coding regions (20p12.3 and 7p22.2) were verified by qPCR. Conclusion: We report the high-resolution rare CNV analysis, revealing novel microdeletions/microduplications in Chinese POI patients. In the selected verified coding regions, we find that the five genes including SYCE1, CYP2E1, NRXN1, PARK2 and CARD11 may be involved in reproduction, thus representing potential candidate genes in POI.

Key words: Menopause, premature, DNA copy number variations, Genomics, Primary ovarian insufficiency, Gene amplification