Autosomal-dominant periodic fever with AA amyloidosis: Novel mutation in tumor necrosis factor receptor 1 gene Rapid communication

Background. The recent identification of genes responsible for syndromes of periodic fever with amyloidosis has opened the way to a molecular diagnosi s of hereditary AA amyloidosis. Methods . A Belgian woman presented for genetic counseling. Three first-deg ree relatives had a diagnosis of renal amyloidosis with a history of recurr ent fever and inflammatory episodes. Medical records and pathological speci mens were obtained from all physicians who had been in charge of her three relatives. Immunohistochemical staining was performed on paraffin-embedded material. A mutation search was performed in the MEFV (Mediterranean fever) and tumor necrosis factor receptor 1 (TNFR1 or TNFRSF1A) genes causing fam iliar Mediterranean fever (FMF) and tumor necrosis factor receptor-associat ed periodic syndrome (TRAPS), respectively. Results. The family history was consistent with autosomal-dominant transmis sion of periodic fever with arthralgias, abdominal pain, and eventual AA am yloidosis involving the kidneys, digestive tract, and thyroid. Recurrent am yloidosis in kidney graft was demonstrated in one patient and was suspected in the other. A novel heterozypous mutation (C55S) in TNFRSF1A was identif ied in the affected patient available for genetic testing but not in the as ymptomatic woman requiring counseling. No mutation was detected in MEFV Conclusions,We report a novel mutation (C55S) in TNFRSF1A, resulting in aut osomal-dominant periodic fever and AA amyloidosis. This condition, known as TRAPS? should be added to the differential diagnosis of hereditary renal a myloidosis, with obvious implications for management and genetic counseling .