Fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family

A French family with hereditary renal amyloidosis (HRA) was studied. The di sease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. Immunohistochemistry studies of glomerular am yloid deposits suggested that the amyloid protein was the fibrinogen A a ch ain. Direct DNA sequencing revealed a G 4993 T transversion and subsequentl y Arg 554 Leu mutation in the fibrinogen Aa chain. This is the first descri ption of this fibrinogen A a alpha chain mutation in Europe. This family, i s of French descent and cannot be related to the previously reported Peruvi an/Mexican and African-American kindreds.