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© 2024. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Whole exome sequencing reveals novel candidate variants for endometriosis utilizing multiple affected members in a single family
Author
Kina, Busra Gizem 1 ; Nura Fitnat Topbas Selcuki 2   VIAFID ORCID Logo  ; Pinar Yalcin Bahat 3 ; Usta, Taner 4 ; Aydin, Sevcan 1 ; Rahmioglu, Nilufer 5 ; Tuncer, Feyza Nur 6   VIAFID ORCID Logo  ; Oral, Engin 7 

 Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey; Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey 
 Department of Obstetrics and Gynecology, Istanbul Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences Turkiye, Istanbul, Turkey 
 Department of Obstetrics and Gynecology, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, University of Health Sciences Turkiye, Istanbul, Turkey 
 Department of Obstetrics and Gynecology, Acibadem Altunizade Hospital, Mehmet Ali Aydinlar University, Istanbul, Turkey 
 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 
 Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey 
 Department of Obstetrics and Gynecology, Bezmialem Vakif University, Istanbul, Turkey 
Section
ORIGINAL ARTICLES
Publication year
2024
Publication date
Jan 2024
Publisher
John Wiley & Sons, Inc.
e-ISSN
23249269
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2919318262
Copyright
© 2024. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.