title: Familial amyloid polyneuropathy associated with TTRSer50Arg mutation in two Iberian families presenting a novel single base change in the mutant gene.
abstract: We present two families, from Spain and Portugal, with familial amyloid polyneuropathy (FAP) associated with the mutation TTRSer50Arg. This mutation was first described in two Japanese patients from independent families and later in a French-Italian patient and a Vietnamese family. The two families presented here, are the first to be diagnosed with this mutation in the Iberian Peninsula. In the patients of both families, FAP was very aggressive as they rapidly developed multiple symptoms with progressive deterioration; we emphasize the presence of severe orthostatic hypotension in the Spanish proband which confined him to a wheelchair. This proband was the first patient with this mutation to have undergone liver transplantation and results were encouraging. The mutation was detected in four patients and one disease-free relative by DNA sequencing of exon 3 and induced mutation restriction analysis. The most outstanding feature was the single base transversion A to C in codon 50 (CGT instead of AGT), whereas in both Japanese patients and the French-Italian patient it was T to G (AGG instead of AGT). To our knowledge only six FAP mutations with more than one single nucleotide mutation for the same codon have been reported to date.
authors.affiliation: Grupo de Estudio de la PAF, Plaza Olivar 5, 07002 Palma de Mallorca, Majorca, Spain. munar-ques@ogm.jazztel.es
authors.forename: Miguel
authors.initials: M
authors.lastname: Munar-Qués
authors.forename: Jaime
authors.initials: J
authors.lastname: Masjuan
authors.forename: Teresa
authors.initials: T
authors.lastname: Coelho
authors.forename: Paul
authors.initials: P
authors.lastname: Moreira
authors.forename: Carlos
authors.initials: C
authors.lastname: Viader-Farré
authors.forename: María J M
authors.initials: MJ
authors.lastname: Saraiva
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D028227:Amyloid Neuropathies, Familial / Q000235:genetics*; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011174:Portugal; D011228:Prealbumin / Q000235:genetics*; D013030:Spain
chemical_list: D003062:Codon; D011228:Prealbumin; D004247:DNA