Mutation analysis of exon 9 of the LDL receptor gene in Thai subjects with primary hypercholesterolemia.
Artigo
em Inglês
| IMSEAR
| ID: sea-44594
ABSTRACT
The low density lipoprotein (LDL) receptor plays an important role in cholesterol homeostasis. A mutation in this gene causes an autosomal codominant disorder, namely familial hypercholesterolemia (FH). In this study, single strand conformation polymorphism (SSCP) analysis was used to screen for mutations in exon 9 of the LDL receptor gene in a group of 45 Thai patients (11 males and 34 females) with primary hypercholesterolemia. The peptide encoded by exon 9 belongs to the epidermal growth factor (EGF) precursor homology domain which is highly conserved in the LDL receptor protein. An abnormal SSCP pattern was observed in one female patient. The same screening strategy was also used to screen DNA samples from 33 normolipidemic subjects. All of these samples showed normal SSCP pattern. By direct DNA sequencing, the underlying mutation in the DNA with abnormal SSCP pattern was identified. The index subject was heterozygous for a T to C transition at nucleotide 1235. This transition would cause a nonconservative substitution of a nonpolar side chain amino acid "methionine" at codon 391, with an uncharged polar side chain amino acid "threonine", note M391T. From multiple amino acid sequence alignment in six species, the amino acid at codon 391 and the others nearby are completely conserved. Such nonconservative substitution of an amino acid residue in a highly conserved region could consequently result in a functional and/or structural defect in the receptor protein. In conclusion, we propose that M391T is likely to be the cause of hypercholesterolemia in this index subject.
Texto completo:
DisponíveL
Índice:
IMSEAR (Sudeste Asiático)
Assunto principal:
Tailândia
/
Feminino
/
Humanos
/
Masculino
/
Receptores de LDL
/
Análise Mutacional de DNA
/
Éxons
/
Polimorfismo Conformacional de Fita Simples
/
Mutação de Sentido Incorreto
/
Hipercolesterolemia
Tipo de estudo:
Estudo prognóstico
País/Região como assunto:
Ásia
Idioma:
Inglês
Ano de publicação:
2000
Tipo de documento:
Artigo
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