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Finnish hereditary amyloidosis is caused by a single nucleotide substitution in the gelsolin gene
Author(s) -
Maury C.P.J.,
Kere J.,
Tolvanen R.,
de la Chapelle A.
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80510-p
Subject(s) - gelsolin , amyloidosis , mutation , microbiology and biotechnology , genetics , oligonucleotide , biology , gene , exon , allele , point mutation , amyloid (mycology) , actin , medicine , pathology , botany
The amyloid protein in Finnish hereditary amyloidosis is a fragment of the actin‐filament binding region of a variant gelsolin molecule. Here we demonstrate, using polymerase chain reaction and allele‐specific oligonucleotide hybridization analyses of genomic DNA, a single base mutation (G 654 → A 654 ) in the gelsolin gene segment encoding the amyloid protein. The mutation is responsible for the expression of the variant (Asn 187 ) gelsolin molecule in Finnish hereditary amyloidosis. The nucleotide substitution was found in all five unrelated patients with Finnish amyloidosis studied, but not in 45 unrelated control subjects. The mutation co‐segregated with the disease phenotype in a family with Finnish amyloidosis. The results show that a single substitution in the gelsolin gene causes Finnish hereditary amyloidosis. The allele‐specific oligonucleotide hybridization method provides a simple and accurate means of detecting this mutation.