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 Bsp1286I 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.
|頁（從 - 到）||649-652|
|期刊||Journal of the Formosan Medical Association|
|出版狀態||已發佈 - 1999 9月|
ASJC Scopus subject areas
- 醫藥 (全部)