FIBRINOGEN A-ALPHA CHAIN LEU-554 - AN AFRICAN-AMERICAN KINDRED WITH LATE-ONSET RENAL AMYLOIDOSIS

An African-American kindred with renal amyloidosis is described Four m embers in two generations developed nephropathy in the sixth to eighth decade of life. Kidney biopsy and subcutaneous fat aspirate biopsy of one patient revealed amyloid deposits. DNA analysis showed that patie nts were heterozygous for a mutation in the fibrinogen Aa chain gene w ith a guanine to thymine transversion at the second base of codon 554, predicting a leucine for arginine substitution Peptide sequence analy sis of isolated plasma fibrinogen showed normal peptide as well as var iant peptide with leucine replacing arginine at position 554, as predi cted by the DNA sequence. The ratio between normal and variant peptide s was approximately I:I in one patient and 3:2 in another. Although th is African-American kindred has the exact same mutation as a previousl y described Peruvian-Mexican kindred, the onset age in this kindred is much later than in the Peruvian-Mexican kindred. This finding may ind icate the existence of additional factor(s) beside the primary causati ve genetic mutation, which affect the expression of the disease.