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- Title
New mutations in non-syndromic primary ovarian insufficiency patients identified via whole-exome sequencing.
- Authors
Patiño, Liliana Catherine; Beau, Isabelle; Carlosama, Carolina; Buitrago, July Constanza; González, Ronald; Suárez, Carlos Fernando; Patarroyo, Manuel Alfonso; Delemer, Brigitte; Young, Jacques; Binart, Nadine; Laissue, Paul
- Abstract
<bold>Study Question: </bold>Is it possible to identify new mutations potentially associated with non-syndromic primary ovarian insufficiency (POI) via whole-exome sequencing (WES)?<bold>Summary Answer: </bold>WES is an efficient tool to study genetic causes of POI as we have identified new mutations, some of which lead to protein destablization potentially contributing to the disease etiology.<bold>What Is Known Already: </bold>POI is a frequently occurring complex pathology leading to infertility. Mutations in only few candidate genes, mainly identified by Sanger sequencing, have been definitively related to the pathogenesis of the disease.<bold>Study Design, Size, Duration: </bold>This is a retrospective cohort study performed on 69 women affected by POI.<bold>Participants/materials, Setting, Methods: </bold>WES and an innovative bioinformatics analysis were used on non-synonymous sequence variants in a subset of 420 selected POI candidate genes. Mutations in BMPR1B and GREM1 were modeled by using fragment molecular orbital analysis.<bold>Main Results and the Role Of Chance: </bold>Fifty-five coding variants in 49 genes potentially related to POI were identified in 33 out of 69 patients (48%). These genes participate in key biological processes in the ovary, such as meiosis, follicular development, granulosa cell differentiation/proliferation and ovulation. The presence of at least two mutations in distinct genes in 42% of the patients argued in favor of a polygenic nature of POI.<bold>Limitations, Reasons For Caution: </bold>It is possible that regulatory regions, not analyzed in the present study, carry further variants related to POI.<bold>Wider Implications Of the Findings: </bold>WES and the in silico analyses presented here represent an efficient approach for mapping variants associated with POI etiology. Sequence variants presented here represents potential future genetic biomarkers.<bold>Study Funding/competing Interest(s): </bold>This study was supported by the Universidad del Rosario and Colciencias (Grants CS/CIGGUR-ABN062-2016 and 672-2014). Colciencias supported Liliana Catherine Patiño´s work (Fellowship: 617, 2013). The authors declare no conflict of interest.
- Subjects
GENETIC mutation; EXOMES; INFERTILITY; HUMAN fertility; ETIOLOGY of diseases
- Publication
Human Reproduction, 2017, Vol 32, Issue 7, p1512
- ISSN
0268-1161
- Publication type
journal article
- DOI
10.1093/humrep/dex089