Alexandre Terré, Magnotti, Jean-Maxime Piot, Guilaine Boursier, Sophie Georgin-Lavialle.
Liink to article: https://doi.org/10.1016/j.ejim.2023.11.014
Summary:
The mutations responsible for the classic form of familial Mediterranean fever (FMF) (recessive, requiring 2 mutations) are located in exon 10 of the MEFV gene.
Mutations in the same MEFV gene have also been reported to be associated with dominant autoinflammatory diseases such as that at position 577, with clinical presentations that differ from classic FMF. The name pyrin-associated autoinflammatory disease (PAAD) was therefore chosen to include all diseases caused by pyrin defects or mutations in the MEFV gene.
Our team has identified a new form of PAAD associated with a dominant somatic mutation of MEFV in a 28-year-old woman of French origin on 3 of her grandparents and Algerian on one. There were no other cases in her family. Since the age of 2, she had suffered recurrent episodes of fever, abdominal pain, erythema of the limbs, particularly the ankles, and joint and muscle pain, with a permanent biological inflammatory syndrome that worsened during febrile crises, with a CRP > 100 mg/L.
In view of the digestive and joint manifestations, and in the absence of joint destruction or any formal element of classification, she was labelled as having atypical Crohn's disease with atypical spondyloarthritis.
A pathogenic Thr577Ala mutation in the MEFV gene with an allele frequency of 16% was found in her; family members were neither carriers nor affected. Somatic mutations are rare "post-zygotic" genetic events occurring after fertilisation. They can occur at any time in life. Mutations are therefore not found in every cell in the body.
This is the first description of a somatic mutation in exon 8 of the MEFV gene responsible for a pyrin-related autoinflammatory dominant disease sensitive to colchicine. She had no further episodes of fever, joint symptoms, abdominal pain or diarrhoea on this treatment. The patient's diagnosis was only made possible by advanced genetic techniques such as high-throughput sequencing and thanks to the expertise of the Montpellier genetics laboratory belonging to the Centre de Référence des Maladies Autoinflammatoires et des Amyloses (CEREMAIA).
Référence :
Alexandre Terré et al. Pyrin-associated autoinflammatory disease with p.Thr577Ala MEFV somatic mutation, European Journal of Internal Medicine.
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