Objective: To analyze DNA from women with premature ovarian failure (POF) for genome-wide copy-number variations (CNVs), focusing on novel autosomal microdeletions.
Design: Case-control genetic association study.
Setting: 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.
Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.