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British kindred with dominant FMF associated with high incidence of AA amyloidosis caused by novel MEFV variant, and a review of the literature

Rowczenio, DM; Youngstein, T; Trojer, H; Omoyinmi, E; Baginska, A; Brogan, P; Papadopoulou, C; ... Lachmann, HJ; + view all (2020) British kindred with dominant FMF associated with high incidence of AA amyloidosis caused by novel MEFV variant, and a review of the literature. Rheumatology , 59 (3) pp. 554-558. 10.1093/rheumatology/kez334. Green open access

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Abstract

OBJECTIVES: Hereditary systemic autoinflammatory diseases are rare genetic disorders, which if untreated, can be complicated by AA amyloidosis leading to renal failure and premature death. Our objective was to find a genetic cause in a British family with a dominantly inherited autoinflammatory disease complicated by AA amyloidosis. METHODS: The index patient and his sister underwent comprehensive clinical and laboratory assessment including the next-generation sequencing panel targeting autoinflammatory genes. Subsequently, other relatives underwent clinical evaluation and genetic testing. Screening of the SAA1 gene was performed in all symptomatic cases. RESULTS: The index case and his sister presented with proteinuria due to AA amyloidosis. They have been suffering from episodes of fever accompanied by severe abdominal and chest pain, arthritis and erythema since childhood. Their father died aged 52 years from complications following a cadaveric renal transplantation. The post-mortem examination demonstrated AA amyloidosis. The index case's grandmother, two paternal cousins and two of their children described similar symptoms. All symptomatic individuals had excellent responses to colchicine. Next-generation sequencing analysis identified a single MEFV p.P373L variant in the index case, his sister and subsequently, in symptomatic family members. Sequencing of the SAA1 gene revealed all cases were heterozygous for the SAA1.1 allele. CONCLUSION: Typically FMF is an autosomal recessive disorder; nonetheless rare cases of dominantly inherited disease have previously been described. Here we report a novel MEFV variant p.P373L, causing dominant FMF complicated by AA amyloidosis in four generations of a British family.

Type: Article
Title: British kindred with dominant FMF associated with high incidence of AA amyloidosis caused by novel MEFV variant, and a review of the literature
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/kez334
Publisher version: https://doi.org/10.1093/rheumatology/kez334
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: MEFV gene, AA amyloidosis, colchicine, familial Mediterranean fever (FMF)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10080250
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