Whole exome sequencing reveals novel candidate variants for endometriosis utilizing multiple affected members in a single family.

Autor: Kina BG; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.; Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey., Topbas Selcuki NF; Department of Obstetrics and Gynecology, Istanbul Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences Turkiye, Istanbul, Turkey., Bahat PY; Department of Obstetrics and Gynecology, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, University of Health Sciences Turkiye, Istanbul, Turkey., Usta T; Department of Obstetrics and Gynecology, Acibadem Altunizade Hospital, Mehmet Ali Aydinlar University, Istanbul, Turkey., Aydin S; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.; Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey., Rahmioglu N; Oxford Endometriosis Care Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK., Tuncer FN; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey., Oral E; Department of Obstetrics and Gynecology, Bezmialem Vakif University, Istanbul, Turkey.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Jan; Vol. 12 (1), pp. e2312. Date of Electronic Publication: 2023 Nov 27.
DOI: 10.1002/mgg3.2312
Abstrakt: Background: Endometriosis is an estrogen-dependent, chronic inflammatory disease that affects 10% of women during the reproductive ages. Despite the estimated 50% heritability for the condition, only 26% was associated with common genetic variants. Thus, necessity of identifying rare variants for the missing heritability is implicated in the literature. Therefore, our study aimed to identify novel rare genetic variants involved in the pathogenesis of endometriosis utilizing a family of multiple affected members.
Methods: A family composed of four affected women along with their two unaffected mothers were recruited at a single gynecology and infertility clinic specialized in endometriosis. All patients presented with endometriomas, which was visualized by transvaginal ultrasonography. Two affected individuals had received laparoscopic endometrioma excision and therefore were diagnosed with recurrent disease. One mother had a history of endometrial serous adenocarcinoma (ESC) for which she underwent hysterectomy with bilateral oophorectomy. Three endometriosis cases were whole exome sequenced on Illumina NextSeq 550 platform with an average of 90% coverage. Candidate genes were confirmed by Sanger sequencing and followed-up with family segregation.
Results: Novel rare variants were identified in TNFRSF1B (NM_001066.3: c.1072G>A, p.(Ala358Thr)) and GEN1 (NM_001130009.3: c.1574C>T, p.(Ser525Leu)) as possible genetic causes of endometriosis. A third novel rare variant was identified in CRABP1 (NM_004378.3:c.54G>C, p.(Glu18Asp)) only on the mother with ESC history and her daughters.
Conclusion: Novel candidate genetic variants that might contribute to endometriosis were suggested that need replication through independent cohorts or validation by functional studies. The family has also received genetic counseling and that the affected daughters are on clinical follow-up, accordingly.
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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