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.