Danish Type Gelsolin–Related Amyloidosis in a Brazilian Family

Abstract

Abstract: : Purpose: Familial amyloidosis of the Finnish type (FAF), is an autosomal dominant form of systemic amyloidosis with a high frequency in Finland but which is very rare in other populations. The main clinical manifestations are corneal lattice dystrophy, progressive cranial and peripheral neuropathy, and skin changes (cutis laxa). The disease is caused by a point mutation, 654G–A, with a substitution of asparagine for aspartic acid at residue 187 in the gelsolin gene (GSN). The Danish–subtype of FAF has previously been described in two families with clinical syndromes similar to FAF and the mutation 654G–T in the GSN gene. This study reports the first case of familial amyloidosis (Danish type) in a Brazilian family caused by a 654 G–T mutation in the gelsolin gene. Methods: Three affected members from two generations of the same family with familial amyloidosis were screened for mutations in the GSN gene. Genomic DNA was extracted from peripheral blood lymphocytes and the polymerase chain reaction (PCR) was carried out under standard conditions using appropriate primers. Direct sequencing of purified PCR products was performed using a DYEnamic^TM ET Terminator Cycle Sequencing Kit from Amersham Biosciences (Piscataway, NJ, USA). Results: Sequence analysis showed the presence of a G to T substitution at nucleotide 654 of the gelsolin gene. This predicts the substitution of tyrosine for the normally occurring aspartic acid at residue 187. Conclusions: The G654T mutation in GSN was identified in the studied family. This is the first report of gelsolin–related familial amyloidosis in a Brazilian family. These results are particularly significant as this pedigree presents an unusual mutation, G654T, that has previously been described only twice (Denmark and Czechoslovakia) in two families with no known Finnish ancestors (Danish type).

Keywords: degenerations/dystrophies • genetics