DNA copy number variations in a cohort of 216 Italian women with premature ovarian failure

Premature ovarian failure (POF) is considered as a multifactorial and heterogeneous condition affecting approximately 1% women of reproductive age. Despite the extensive research, the considerably complex pathogenesis of POF is still not well understood. POF can develop as result of a broad spectrum of pathogenic mechanisms including genetic, autoimmune and iatrogenic causes that leads to follicular dysfunction or depletion. In recent years, many research studies are trying to find out the genetic component of the disease by using different high-resolution methods. We have performed a case-control genetic association study, using high-resolution SNP microarrays to investigate DNA copy number variations (CNVs) of 216 Italian women presenting POF phenotype and 240 women from the Italian general population as a control. All patient and control samples were collected at the Division of Genetics and Cell Biology, San Raffaele Scientific Institute and University of Milan, Italy and genotyped by Illumina PsychArray BeadChips at the Estonian Genome Center University of Tartu Genotyping core in Tartu, Estonia. Microarray data, analyzed using different algorithms, revealed both, genomic regions containing genes previously associated with POF (e.g. 26.8Mb 1q41-q44 duplication affecting FMN2 gene) and novel potentially clinically significant CNVs (e.g. 11p15.2 microdeletion). In addition to autosomal CNVs, we identified several POF critical regions on the X chromosome. The currently known POF genes only account for a small proportion of patients, while the majority remain without a genetic diagnosis. Using whole-genome DNA microarrays, the present study provides novel insight into the implications of CNVs in genetic aetiology of POF.