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

Pediatric Research (2024)Cite this article

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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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Author information

Author notes

  1. These authors contributed equally: Aasem Abu Shtaya, Naama Orenstein.

Authors and Affiliations

  1. Recanati Genetic Institute, Rabin Medical Center—Beilinson Hospital, Petach Tikva, Israel

    Aasem Abu Shtaya, Lily Bazak, Gabriel Lidzbarsky, Marina Lifshitc Kalis, Noa Ruhrman Shahar & Lina Basel-Salmon

  2. Unit of Gastroenterology, Carmel Medical Center, Haifa, Israel

    Aasem Abu Shtaya

  3. Pediatric Genetics Unit, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

    Naama Orenstein, Efrat Sofrin-Drucker, Ranit Jaron, Nesia Kropach Gilad & Lina Basel-Salmon

  4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Naama Orenstein, Gil Amarilyo, Efrat Sofrin-Drucker, Nesia Kropach Gilad & Lina Basel-Salmon

  5. Rheumatology Department, Schneider Children’s Medical Centre, Petach Tikvah, Israel

    Gil Amarilyo

  6. Felsenstein Medical Research Center, Petach Tikva, Israel

    Lina Basel-Salmon

Authors
  1. Aasem Abu Shtaya
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  11. Lina Basel-Salmon
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Contributions

All author has met the Pediatric Research authorship requirements as listed below. Aasem Abu Shtaya, Naama Orenstein, Lily Bazak, Gabriel Lidzbarsky, Marina Lifshitc Kalis Efrat Sofrin-Drucker, Ranit Jaron, Noa Ruhrman Shahar and Nesia Kropach Gilad made. Substantial contributions to conception and design, acquisition of data, analysis and interpretation of data of this manuscript. Aasem Abu Shtaya and Naama Orenstein significantly contributed to drafting the article and revising it critically for important intellectual content. Aasem Abu Shtaya and Lina Basel-Salmon made the final approval of the version to be published.

Corresponding author

Correspondence to Aasem Abu Shtaya.

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The authors declare no competing interests.

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All parents of participated children signed a written consent for participation in this study.

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Abu Shtaya, A., Orenstein, N., Bazak, L. et al. High frequency of MEFV disease-causing variants in children with very-early-onset inflammatory bowel disease. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03242-z

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