Cengiz Karakaya1,2, Aylin Pelin Çil3, Kaya Bilguvar4,5,6, Tunahan Çakir7, Mete Hakan Karalok2, Recep Onur Karabacak8, Ahmet Okay Caglayan5,9,10. 1. Department of Medical Biochemistry, Gazi University School of Medicine, Ankara, Turkey. 2. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA. 3. American Hospital Women's Health and Assisted Reproductive Center Guzelbahce Sok, İstanbul, Turkey. 4. Department of Genetics, Yale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut, USA. 5. Departments of Neurosurgery, Neurobiology and Genetics, Yale School of Medicine, New Haven, Connecticut, USA. 6. Department of Medical Genetics, Acibadem University School of Medicine, Istanbul, Turkey. 7. Department of Bioengineering, Gebze Technical University, Gebze, Turkey. 8. Department of Obstetrics and Gynecology, Gazi University Faculty of Medicine, Ankara, Turkey. 9. Department of Medical Genetics, School of Medicine, Dokuz Eylul University, Izmir, Turkey. 10. Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
Abstract
AIM: To identify pathogenic rare coding Mendelian/high-effect size variant(s) by whole-exome sequencing in familial polycystic ovary syndrome (PCOS) patients to elucidate PCOS-related pathways. METHODS: Twenty women and their affected available relatives diagnosed with PCOS according to Rotterdam criteria were recruited. Whole-exome sequencing on germ-line DNA from 31 PCOS probands and their affected relatives was performed. Whole-exome sequencing data were further evaluated by pathway and chemogenomics analyses. In-slico analysis of candidate variants were done by VarCards for functional predictions and VarSite for impact on three-dimensional (3D) structures in the candidate proteins. RESULTS: Two heterozygous rare FBN3 missense variants in three patients, and one FN1 missense variant in one patient from three different PCOS families were identified. CONCLUSION: We identified three novel FBN3 and FN1 variants for the first time in the literature and linked with PCOS. Further functional studies may identify causality of these newly discovered PCOS-related variants, and their role yet remains to be investigated. Our findings may improve our understanding of the biological pathways affected and identify new drug targets.
AIM: To identify pathogenic rare coding Mendelian/high-effect size variant(s) by whole-exome sequencing in familial polycystic ovary syndrome (PCOS) patients to elucidate PCOS-related pathways. METHODS: Twenty women and their affected available relatives diagnosed with PCOS according to Rotterdam criteria were recruited. Whole-exome sequencing on germ-line DNA from 31 PCOS probands and their affected relatives was performed. Whole-exome sequencing data were further evaluated by pathway and chemogenomics analyses. In-slico analysis of candidate variants were done by VarCards for functional predictions and VarSite for impact on three-dimensional (3D) structures in the candidate proteins. RESULTS: Two heterozygous rare FBN3 missense variants in three patients, and one FN1 missense variant in one patient from three different PCOS families were identified. CONCLUSION: We identified three novel FBN3 and FN1 variants for the first time in the literature and linked with PCOS. Further functional studies may identify causality of these newly discovered PCOS-related variants, and their role yet remains to be investigated. Our findings may improve our understanding of the biological pathways affected and identify new drug targets.
Authors: D R Stewart; B A Dombroski; M Urbanek; W Ankener; K G Ewens; J R Wood; R S Legro; J F Strauss; A Dunaif; R S Spielman Journal: J Clin Endocrinol Metab Date: 2006-07-25 Impact factor: 5.958
Authors: R Koivunen; A Pouta; S Franks; H Martikainen; U Sovio; A-L Hartikainen; M I McCarthy; A Ruokonen; A Bloigu; M-R Järvelin; L Morin-Papunen Journal: Hum Reprod Date: 2008-06-10 Impact factor: 6.918
Authors: Hannah Carter; Christopher Douville; Peter D Stenson; David N Cooper; Rachel Karchin Journal: BMC Genomics Date: 2013-05-28 Impact factor: 3.969