Romano-Ward long QT syndrome: identification of a HERG mutation in a Taiwanese kindred.
J Formos Med Assoc
; 98(9): 649-52, 1999 Sep.
Article
em En
| MEDLINE
| ID: mdl-10560244
ABSTRACT
Romano-Ward syndrome is an autosomal dominant long-QT syndrome (LQTS) that predisposes affected individuals to sudden death from tachyarrhythmias. We investigated the molecular basis of LQTS in a Taiwanese kindred. Clinical and genetic analyses revealed that a mutation was linked to the human ether-a-go-go-related gene (HERG). The coding sequences and exon-intron borders of HERG were amplified by means of polymerase chain reaction and subjected to single-strand conformation polymorphism (SSCP) analysis. An exon with an aberrant SSCP pattern was cloned and sequenced to study the molecular lesion. A C-->T transition in codon 614, leading to substitution of a valine for an alanine residue in the pore region of the HERG protein, was identified. Analysis with Bsp12861 endonuclease digestion showed the mutation to be present in all affected family members. Given that an unaffected paternal uncle had inherited the same allele from the grandfather as the proband's father, a de novo mutation had apparently occurred in the father and was transmitted to his offspring. In addition to offering presymptomatic genetic diagnosis, identification of the disease-causing mutation may suggest new therapeutic approaches for treatment and prevention of this cardiovascular disease.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do QT Longo
/
Canais de Potássio
/
Transativadores
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
/
Proteínas de Transporte de Cátions
/
Proteínas de Ligação a DNA
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article