OBJECTIVE: To identify new molecular actors involved in nonsyndromic premature ovarian failure (POF) etiology. DESIGN: This is a retrospective case-control cohort study. SETTING: University research group and IVF medical center. PATIENT(S): Twelve women affected by nonsyndromic POF. The control group included 176 women whose menopause had occurred after age 50 and had no antecedents regarding gynecological disease. A further 345 women from the same ethnic origin (general population group) were also recruited to assess allele frequency for potentially deleterious sequence variants. INTERVENTION(S): Next generation sequencing (NGS), Sanger sequencing, and bioinformatics analysis. MAIN OUTCOME MEASURE(S): The complete coding regions of 70 candidate genes were massively sequenced, via NGS, in POF patients. Bioinformatics and genetics were used to confirm NGS results and to identify potential sequence variants related to the disease pathogenesis. RESULT(S): We have identified mutations in two novel genes, ADAMTS19 and BMPR2, that are potentially related to POF origin. LHCGR mutations, which might have contributed to the phenotype, were also detected. CONCLUSION(S): We thus recommend NGS as a powerful tool for identifying new molecular actors in POF and for future diagnostic/prognostic purposes.
OBJECTIVE: To identify new molecular actors involved in nonsyndromic premature ovarian failure (POF) etiology. DESIGN: This is a retrospective case-control cohort study. SETTING: University research group and IVF medical center. PATIENT(S): Twelve women affected by nonsyndromic POF. The control group included 176 women whose menopause had occurred after age 50 and had no antecedents regarding gynecological disease. A further 345 women from the same ethnic origin (general population group) were also recruited to assess allele frequency for potentially deleterious sequence variants. INTERVENTION(S): Next generation sequencing (NGS), Sanger sequencing, and bioinformatics analysis. MAIN OUTCOME MEASURE(S): The complete coding regions of 70 candidate genes were massively sequenced, via NGS, in POFpatients. Bioinformatics and genetics were used to confirm NGS results and to identify potential sequence variants related to the disease pathogenesis. RESULT(S): We have identified mutations in two novel genes, ADAMTS19 and BMPR2, that are potentially related to POF origin. LHCGR mutations, which might have contributed to the phenotype, were also detected. CONCLUSION(S): We thus recommend NGS as a powerful tool for identifying new molecular actors in POF and for future diagnostic/prognostic purposes.
Authors: Matthew S Bramble; Ellen H Goldstein; Allen Lipson; Tuck Ngun; Ascia Eskin; Jason E Gosschalk; Lara Roach; Neerja Vashist; Hayk Barseghyan; Eric Lee; Valerie A Arboleda; Daniel Vaiman; Zafer Yuksel; Marc Fellous; Eric Vilain Journal: Hum Reprod Date: 2016-02-23 Impact factor: 6.918
Authors: Triin Laisk-Podar; Cecilia M Lindgren; Maire Peters; Juha S Tapanainen; Cornelis B Lambalk; Andres Salumets; Reedik Mägi Journal: Trends Endocrinol Metab Date: 2016-05-21 Impact factor: 12.015
Authors: JoAnne S Richards; Yi A Ren; Nicholes Candelaria; Jaye E Adams; Aleksandar Rajkovic Journal: Endocr Rev Date: 2018-02-01 Impact factor: 19.871
Authors: Sarah Eskenazi; Anne Bachelot; Justine Hugon-Rodin; Genevieve Plu-Bureau; Anne Gompel; Sophie Catteau-Jonard; Denise Molina-Gomes; Didier Dewailly; Catherine Dodé; Sophie Christin-Maitre; Philippe Touraine Journal: J Endocr Soc Date: 2021-03-01
Authors: Asma Sassi; Julie Désir; Véronique Janssens; Martina Marangoni; Dorien Daneels; Alexander Gheldof; Maryse Bonduelle; Sonia Van Dooren; Sabine Costagliola; Anne Delbaere Journal: F S Rep Date: 2020-08-22