Genomic analysis using high-resolution single-nucleotide polymorphism arrays reveals novel microdeletions associated with premature ovarian failure.
OBJECTIVE
To analyze DNA from women with premature ovarian failure (POF) for genome-wide copy-number variations (CNVs), focusing on novel autosomal microdeletions.


METHODS
Case-control genetic association study.


METHODS
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.


METHODS
Of 89 POF patients, eight experienced primary amenorrhea and 81 exhibited secondary amenorrhea before age 40 years.


METHODS
Genomic DNA from peripheral blood samples was analyzed for CNVs using high-resolution single-nucleotide polymorphism (SNP) arrays.


METHODS
Identification of novel CNVs in 89 POF cases, using the Database of Genomic Variants as a control population.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Megan M
MM
McGuire
Wayne
W
Bowden
Natalie J
NJ
Engel
Hyo Won
HW
Ahn
Ertug
E
Kovanci
Aleksandar
A
Rajkovic
D000328:Adult; D016022:Case-Control Studies; D002872:Chromosome Deletion; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D055815:Young Adult
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