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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10767589PMC
http://dx.doi.org/10.1002/mgg3.2312DOI Listing

Publication Analysis

Top Keywords

genetic variants
12
novel rare
12
novel candidate
8
endometriosis utilizing
8
rare variants
8
endometriosis
7
variants
6
novel
5
family
5
genetic
5

Similar Publications

Background: Aicardi-Goutières Syndrome is a monogenic type 1 interferonopathy with infantile onset, characterized by a variable degree of neurological damage. Approximately 7% of Aicardi-Goutières Syndrome cases are caused by pathogenic variants in the ADAR gene and are classified as Aicardi-Goutières Syndrome type 6. Here, we present a new homozygous pathogenic variant in the ADAR gene.

View Article and Find Full Text PDF

Background: Epistasis, the phenomenon where the effect of one gene (or variant) is masked or modified by one or more other genes, significantly contributes to the phenotypic variance of complex traits. Traditionally, epistasis has been modeled using the Cartesian epistatic model, a multiplicative approach based on standard statistical regression. However, a recent study investigating epistasis in obesity-related traits has identified potential limitations of the Cartesian epistatic model, revealing that it likely only detects a fraction of the genetic interactions occurring in natural systems.

View Article and Find Full Text PDF

Introduction: Cryptorchidism impairs sperm development and increases the risk of infertility and testicular cancer. Estrogen signalling is critical for proper descent of the testicles, and hormonal imbalances play a role in cryptorchidism. CYP19, also known as aromatase, encodes an enzyme that converts testosterone, a male sex hormone, into estradiol, the main form of estrogen.

View Article and Find Full Text PDF

Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140.

Am J Kidney Dis

December 2024

Service de Néphrologie, Hémodialyse et Transplantation Rénale, Centre de référence MARHEA, CHRU Brest, Brest, France; Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Brussels, Belgium. Electronic address:

Rationale & Objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study Design: Case series.

View Article and Find Full Text PDF

Loss-of-function SLC25A20 mutation causes carnitine-acylcarnitine translocase deficiency by reducing SLC25A20 protein stability.

Gene

December 2024

Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou 510515, China; Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address:

Background/aim: Autosomal-recessive carnitine-acylcarnitine translocase deficiency (CACTD) is a rare disorder of long-chain fatty acid oxidation caused by variants in the SLC25A20 gene. Under fasting conditions, most newborns with severe CACTD experience sudden cardiac arrest and hypotonia, often leading to premature death due to rapid disease progression. Understanding of genetic factors and pathogenic mechanisms in CACTD is essential for its diagnosis, treatment, and prevention.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!