High Frequency of MEFV Disease-causing Variants in Children with Very-early-onset Inflammatory Bowel Disease

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2024 May 11

PMID 38734812

Authors

Aasem Abu Shtaya

Naama Orenstein

Lily Bazak

Gabriel Lidzbarsky

Marina Lifshitc Kalis

Gil Amarilyo

Efrat Sofrin-Drucker

Ranit Jaron

Noa Ruhrman Shahar

Nesia Kropach Gilad

Lina Basel-Salmon

Affiliations

Soon will be listed here.

Abstract

Background: Biological similarities between inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) have been described in humans and animal models suggesting a possible common genetic basis. FMF is caused by variants in the MEFV gene which encodes pyrin, an immune regulator. This study aimed to investigate the carrier rate of disease-causing MEFV variants in children of different ethnicities diagnosed with very-early-onset IBD (VEO-IBD).

Methods: The study included 23 children diagnosed with VEO-IBD who had undergone whole exome sequencing. The exomes were evaluated for MEFV monoallelic and biallelic disease-causing variants and compared to exome sequencing data of 250 probands with suspected monogenic diseases other than IBD.

Results: Of the 23 children diagnosed with VEO-IBD, 12 (52%) were carriers of at least one MEFV disease-causing variant, which was threefold higher than in individuals without IBD. The most frequent variants identified were p.M694V and p.E148Q (42% each). The allelic frequency of MEFV variants was found to be higher across the VEO-IBD group in 13 of 14 ethnicities compared to the control group.

Conclusion: The study suggests that disease-causing variants in the MEFV gene should be sought in cases of VEO-IBD. However, the clinical importance of this finding is yet to be defined.

Impact: There are biological similarities between inflammatory bowel disease and familial Mediterranean fever, suggesting a possible genetic relationship. Children less than 6 years old clinically diagnosed with inflammatory bowel disease have a threefold higher rate of disease-causing variants in the MEFV gene than controls. Monogenic testing in children with very-early-onset inflammatory bowel disease should include a search for MEFV variants.

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