High frequency of MEFV disease-causing variants in children with very-early-onset inflammatory bowel disease

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalPediatric Research
Early online date11 May 2024
DOIs
StateE-pub ahead of print - 11 May 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2024.

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