Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling
<p dir="ltr">Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (<i>MEFV)</i> gene. Despite a typical clinical expression, many patients have either a single...
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2020
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| Summary: | <p dir="ltr">Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (<i>MEFV)</i> gene. Despite a typical clinical expression, many patients have either a single or no mutation in <i>MEFV</i>. The current work is aimed to revisit the genetic landscape of FMF disease using high-coverage whole genome sequencing. In atypical patients (carrying a single or no mutation in <i>MEFV</i>), we revealed many rare variants in genes associated with auto-inflammatory disorders, and more interestingly, we discovered a novel variant ( a 2.1-Kb deletion) in exon 11 of <i>IL1RL1</i> gene, present only in patients. To validate and screen this patient-specific variant, a tandem of allele-specific PCR and quantitative real-time PCR was performed in 184 FMF patients and 218 healthy controls and we demonstrated that the novel deletion was absent in controls and was present in more than 19% of patients. This study sheds more light on the mutational landscape of FMF. Our discovery of a disease-specific variant in <i>IL1RL1</i> gene may constitute a novel genetic marker for FMF. This finding suggesting a potential role of the IL33/ST2 signalling in the disease pathogenicity highlights a new paradigm in FMF pathophysiology.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.15701" target="_blank">http://dx.doi.org/10.1111/jcmm.15701</a></p> |
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