Screening and biochemical characterization of transthyretin variants in the Portuguese population

• Tipo: Artigo em Revista Científica Internacional
• Data: 1997

Autores

Alves, IL (Autor) Outra; Altland, K (Autor) Outra; Almeida, MR (Autor) ICBAS; Winter, P (Autor) Outra; Saraiva, MJM (Autor) ICBAS

Revista

Título: Human Mutation

Vol. 9

Páginas: 226-233

ISSN: 1059-7794

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 41 Citações

Scopus - 48 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências da terra e ciências do ambiente

Outras Informações

ID Authenticus: P-001-CGC

DOI: 10.1002/(sici)1098-1004(1997)9:3<226::aid-humu3>3.0.co;2-5

Abstract (EN): The study of pathogenic and nonpathogenic transthyretin (TTR) variants is very important for the understanding of such TTR related diseases as hereditary amyloidosis and also to establish a relationship between the structure and function of the molecule. Variants with clinical manifestations can be easily detected, but clinically silent variants can be detected only by population screening programs using specialized techniques. Hybrid isoelectric focusing (HIEF) in extremely flattened immobilized pH gradients (IPG) allows the detection of even neutral aminoacid substitutions and has been used to analyze similar to 5,000 samples from the Portuguese population. Comparison with samples from carriers of three known TTR mutations (Met 30 associated with hereditary amyloidosis, Met 119, and Asn 90) was also made. In this study we detected: (1) 8 individuals carriers of TTR Met 30, (2) 35 carriers of TTR Met 119, (3) 12 carriers of TTR Asn 90, (4) 1 compound heterozygote for TTR Met 30/Met 119, and (5) 5 variants that presented a different pattern from the controls used, We also performed DNR sequencing analyses of two of the variants with the different band pattern in HIEF. The individuals were found to be carriers of TTR Ile 122 and TTR Thr 109, respectively. All the mutations detected, except for Asn 90, result from substitutions in CpG hot spots and thus can be rather frequent in the populations. Studies on the clinical evolution of the compound heterozygotes and on the physical chemical properties of these hybrid TTRs will help to understand the pathogenicity associated with TTR. (C) 1997 Wiley-Liss, Inc.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8