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 diagnosis of hereditary AA amyloidosis. Methods . A Belgian woman presented for genetic counseling. Three first-degree relatives had a diagnosis of renal amyloidosis with a history of recurrent fever and inflammatory episodes. Medical records and pathological specimens 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 familiar Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively. Results. The family history was consistent with autosomal-dominant transmission of periodic fever with arthralgias, abdominal pain, and eventual AA amyloidosis involving the kidneys, digestive tract, and thyroid. Recurrent amyloidosis in kidney graft was demonstrated in one patient and was suspected in the other. A novel heterozypous mutation (C55S) in TNFRSF1A was identified in the affected patient available for genetic testing but not in the asymptomatic woman requiring counseling. No mutation was detected in MEFV Conclusions,We report a novel mutation (C55S) in TNFRSF1A, resulting in autosomal-dominant periodic fever and AA amyloidosis. This condition, known as TRAPS? should be added to the differential diagnosis of hereditary renal amyloidosis, with obvious implications for management and genetic counseling.