Renal apolipoprotein A-I amyloidosis associated with a novel mutant Leu64Pro.
Apolipoprotein A-I amyloidosis (Apo A-I) is an inherited systemic disease that results from the pathologic deposition in tissues throughout the body of fibrils composed of Apo A-I-related molecules. This disorder has been linked to mutations occurring within the coding region of the Apo A-I gene and, to date, 11 such substitutions have been documented. In 4 of these cases, the kidney was the target organ of the disease process. The authors report their studies on a patient with renal amyloidosis and a heretofore undescribed alteration in the amyloidogenic precursor protein. Analyses of genomic DNA evidenced a transition in the second base of codon 64 (T-->C) in one Apo A-I allele that resulted in the replacement of leucine by proline at position 64 (Leu64Pro). Additionally, fibrils extracted from the kidney and characterized chemically were found to be composed almost exclusively of an approximately 96-residue N-terminal Apo A-I fragment that contained the Leu64Pro substitution. These studies have provided further evidence for Apo A-I amyloidogenicity and the propensity of certain mutants to deposit in renal parenchyma.
Murphy
Charles L
CL
Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
Wang
Shuching
S
Weaver
Kristal
K
Gertz
Morie A
MA
Weiss
Deborah T
DT
Solomon
Alan
A
D019943:Amino Acid Substitution / Q000235:genetics; D028226:Amyloidosis, Familial / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology*; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics*
D016632:Apolipoprotein A-I; D011392:Proline; D007930:Leucine