title: Mutation and transcription analysis of transthyretin gene in Italian families with hereditary amyloidosis: a putative novel hot spot' in codon 47.
abstract: Transthyretin gene mutations are associated with autosomal dominant familial amyloidosis. The commonest phenotype in the patients is peripheral neuropathy, but restrictive cardiomyopathy is also a frequent sign. More than 70 different mutations in the gene have been described. Although these mutations are randomly distributed, some hot spots have also been reported notably at position 6, 30, 33, 58, 109, 119 and 122. A few of these codons contain a CpG dinucleotide. We describe an additional 'hot spot' occurring at codon 47, in which we report one novel and two previously described mutations. This codon, however, does not contain a CpG dinucleotide, suggesting that other mechanisms might be responsible for the allelic heterogeneity. All the reported mutations in codon 47 are located in the exon 2 consensus sequence and are potentially involved in splicing. We performed transcription analysis on two livers obtained from transplanted patients carrying the Ala47 mutation. These livers showed a normally spliced message, indicating that this mutation does not affect splicing.
authors.affiliation: Istituto di Genetica Medica, Università di Ferrara, Italy. fla@olns.unife.it
authors.forename: A
authors.initials: A
authors.lastname: Ferlini
authors.forename: L
authors.initials: L
authors.lastname: Obici
authors.forename: E
authors.initials: E
authors.lastname: Manzati
authors.forename: O
authors.initials: O
authors.lastname: Biadi
authors.forename: E
authors.initials: E
authors.lastname: Tarantino
authors.forename: P
authors.initials: P
authors.lastname: Conigli
authors.forename: G
authors.initials: G
authors.lastname: Merlini
authors.forename: M
authors.initials: M
authors.lastname: D'Alessandro
authors.forename: V
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: C A
authors.initials: CA
authors.lastname: Tassinari
authors.forename: F
authors.initials: F
authors.lastname: Salvi
mesh_terms: D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D003062:Codon; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011228:Prealbumin / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D003062:Codon; D017931:DNA Primers; D011228:Prealbumin; D012333:RNA, Messenger; D001120:Arginine