Xiang Yang1,2,3, Philippe Touraine4,5, Swapna Desai1, Gregory Humphreys6, Huaiyang Jiang1, Alexander Yatsenko1, Aleksandar Rajkovic7,8. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA. 2. The Third Xiangya Hospital, Central South University, Changsha, China. 3. Department of Gynecology, The Second Xiangya Hospital, Central South University, Changsha, China. 4. Department of Endocrinology and Reproductive Medicine, Centre des Maladies Endocriniennes Rares de la Croissance et du Développement, Centre des Pathologies Gynécologiques Rares, Paris, France. 5. Pitie Salpetriere Hospital, Sorbonne Université, Paris, France. 6. Magee-Womens Hospital, Pittsburgh, PA, USA. 7. Department of Pathology, University of California, San Francisco, CA, 94143-0794, USA. aleks.rajkovic@ucsf.edu. 8. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA. aleks.rajkovic@ucsf.edu.
Abstract
PURPOSE: To investigate the potential genetic etiology of premature ovarian insufficiency (POI). METHODS: Whole-exome sequencing (WES) was done on DNA samples from women diagnosed with POI. Mutations identified were analyzed by in silico tools and were annotated according to the guidelines of the American College of Medical Genetics and Genomics. Plausible variants were confirmed by Sanger sequencing. RESULTS: Four of the 33 individuals (12%) carried pathogenic or likely pathogenic variants, and 6 individuals carried variants of unknown significance. The genes identified with pathogenic or likely pathogenic variants included PMM2, MCM9, and PSMC3IP. CONCLUSIONS: WES is an efficient tool for identifying gene variants in POI women; however, interpretation of variants is hampered by few exome studies involving ovarian disorders and the need for trio sequencing to determine inheritance and to detect de novo variants.
PURPOSE: To investigate the potential genetic etiology of premature ovarian insufficiency (POI). METHODS: Whole-exome sequencing (WES) was done on DNA samples from women diagnosed with POI. Mutations identified were analyzed by in silico tools and were annotated according to the guidelines of the American College of Medical Genetics and Genomics. Plausible variants were confirmed by Sanger sequencing. RESULTS: Four of the 33 individuals (12%) carried pathogenic or likely pathogenic variants, and 6 individuals carried variants of unknown significance. The genes identified with pathogenic or likely pathogenic variants included PMM2, MCM9, and PSMC3IP. CONCLUSIONS: WES is an efficient tool for identifying gene variants in POI women; however, interpretation of variants is hampered by few exome studies involving ovarian disorders and the need for trio sequencing to determine inheritance and to detect de novo variants.
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