Hereditary amyloidosis of an unusual form has been reported in two separate kindreds; one was Polish-Canadian and the other was Irish-American. In both kindreds, affected members developed hypertension and nephrotic syndrome due to amyloidosis in their forties or fifties, but the genetic background responsible for the condition has been left undetermined. To identify the genetic defect in these kindreds, a portion of exon 5 of the fibrinogen α-chain gene in members of these kindreds was examined for a mutation by single-strand conformation polymorphism analysis and direct DNA sequencing. DNA analyses revealed an A→T transversion at the second base of codon 526 of the fibrinogen α-chain gene in both of these kindreds. Analysis of DNA polymorphisms in the fibrinogen a-chain gene locus (TCTT repeat in intron 3, Rsal site in exon 5, and Taql site in the 3' flanking region of the gene) showed the haplotype B5-Rsal(+)-Taql(-) for the Val 526 mutant gene in both kindreds studied here, as well as in two kindreds previously described. The fibrinogen α-chain gene mutation (Val 526) is the genetic defect responsible for hereditary renal amyloidosis in these two kindreds, and the mutant genes in the Val 526 kindreds may have been derived from a single founder.
|Original language||English (US)|
|Number of pages||6|
|Journal||QJM - Monthly Journal of the Association of Physicians|
|State||Published - Oct 1996|
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