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

Busra Gizem Kina, Nura Fitnat Topbaş Selçuki, Pinar Yalcin Bahat, Pınar Yalçın Bahat, Taner Usta, Sevcan Aydin, Sevcan Aydın, Nilüfer Rahmioğlu, Nilufer Rahmioglu, Feyza Nur Tuncer, Engin Oral
Molecular genetics & genomic medicine · 2023 · vol. 12(1) , pp. e2312 · doi:10.1002/mgg3.2312 · PMID:38013616 · PMC10767589 · W4389093968
article OA: gold CC0 ⤵ 2 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Whole exome sequencing of an endometriosis-affected family identified novel rare variants in TNFRSF1B and GEN1, with a variant in CRABP1 identified in affected daughters and their mother with a history of endometrial cancer.

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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.

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Condition tags

endometriosisendometriomainfertility

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Exome Exome Exome Exome Exome Exome Sequencing Exome Sequencing Exome Sequencing Exome Sequencing Exome Sequencing Female Female Female Female

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