The molecular basis of renal amyloidosis in Irish–American and Polish–Canadian kindreds

Hereditary amyloidosis of an unusual form has been reported in two separate kindreds; one was Polish–Canadian and the other was Irish–American (Am J Med 1975; 59:121 and Trans Assoc Am Physicians 1981; 94: 211). In both kindreds, affected members developed hypertension and nephrotic syndrome due to...

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Bibliographic Details
Published in:QJM : An International Journal of Medicine 1996-10, Vol.89 (10), p.745-750
Main Authors: Uemichi, T., Liepnieks, J.J., Alexander, F., Benson, M.D.
Format: Article
Language:English
Subjects:
Adult
Aged
Amyloidosis
Amyloidosis - genetics
Biological and medical sciences
Female
Fibrinogens, Abnormal - genetics
Fibrinogens, Abnormal - physiology
Humans
Kidney Diseases - genetics
Medical sciences
Metabolic diseases
Microsatellite Repeats
Middle Aged
Other metabolic disorders
Pedigree
Point Mutation
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Polymorphism, Single-Stranded Conformational
Sequence Analysis, DNA
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Summary:Hereditary amyloidosis of an unusual form has been reported in two separate kindreds; one was Polish–Canadian and the other was Irish–American (Am J Med 1975; 59:121 and Trans Assoc Am Physicians 1981; 94: 211). 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 α-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 (J Clin Invest 1994; 93: 731). 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.
ISSN:1460-2725
1460-2393
DOI:10.1093/qjmed/89.10.745