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High frequency of MEFV disease-causing variants in children with very-early-onset inflammatory bowel disease
Aasem Abu Shtaya1,2, Naama Orenstein3,4, Lily Bazak5
1Recanati Genetic Institute, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel. aasemab@hotmail.com.
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.
Insights
Children with very-early-onset inflammatory bowel disease (VEO-IBD) show a threefold higher carrier rate for disease-causing MEFV gene variants. Genetic testing for MEFV variants is recommended in VEO-IBD cases.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Biological similarities exist between inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF).
- Familial Mediterranean fever is linked to variants in the MEFV gene, which regulates immune responses.
- Investigating MEFV variant carrier rates in VEO-IBD offers insight into potential shared genetic factors.
Purpose of the Study:
- To determine the carrier frequency of disease-causing MEFV variants in children with very-early-onset IBD (VEO-IBD).
- To compare MEFV variant carrier rates between VEO-IBD patients and a control group across diverse ethnicities.
Main Methods:
- Whole exome sequencing was performed on 23 children diagnosed with VEO-IBD.
- MEFV monoallelic and biallelic disease-causing variants were analyzed.
- VEO-IBD exome data was compared with 250 controls with suspected monogenic diseases.
Main Results:
- Over half (52%) of VEO-IBD patients carried at least one MEFV disease-causing variant.
- This carrier rate was threefold higher than in the control group.
- The most common variants were p.M694V and p.E148Q; higher allelic frequencies were observed in VEO-IBD across 13 ethnicities.
Conclusions:
- Disease-causing MEFV variants should be considered in the genetic evaluation of VEO-IBD.
- The clinical significance of MEFV variants in VEO-IBD requires further investigation.
- Monogenic testing for VEO-IBD should include MEFV variants due to potential genetic links.
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