The spectrum of transthyretin gene mutations in italy: a report

Abstract

Transthyretin gene mutations causing autosomal dominant familial amyloidotic polyneuropathy (FAP) are often associated with cardiomyopathy. More than 80 amino acid variations have been described until now, showing a high allelic heterogeneity. We screened for TTR mutations 55 patients with mixed polyneuropathy with variable cardiac involvement. By means of direct sequencing of the full coding region we identified the following 26 genotypes: 2 Ser6 (polymorphism), 3 Met30, 4 Gln89, 2 Leu64 (TTT > TTG) and 7 Leu64 (TTT > CTT), 2 Ala49, 2 Leu68, 1 Thr34, 1 Arg50, 1 Glu53 and 1 Asn90. Interestingly, two Leu64 variants were due to a novel nucleotide variation TTT to TTG in codon 64 and 1 Asn90 mutation was found to co‐segregate with a FAP phenotype. Transthyretin mutations in hereditary amyloidosis deserve to be investigated in all cases of mixed polyneuropathy with cardiomyopathy both familial and sporadic. A marked allelic heterogeneity in Italy has been further confirmed by this study and PCR and direct sequencing seems to represent the more appropriate diagnostic tool for this pathology.