Finnish hereditary amyloidosis is caused by a single nucleotide substitution in the gelsolin gene

FEBS Letters

Maury, C.P.J.¹  de la Chapelle, A.¹  Kere, J.¹  Tolvanen, R.¹ 

[1] Fourth Department of Medicine and Department of Medical Genetics, University of Helsinki, Helsinki, Finland

关键词: Finnish hereditary amyloidosis;    Familial amyloid polyneuropathy;    Gelsolin gene;    Point mutation;    Oligonucleotide hybridization;    DNA-test;   

DOI  :  10.1016/0014-5793(90)80510-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (G⁶⁵⁴ → A⁶⁵⁴) in the gelsolin gene segment encoding the amyloid protein. The mutation is responsible for the expression of the variant (Asn¹⁸⁷) 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.

【 授权许可】

Unknown