Abstract | BACKGROUND: METHODS AND RESULTS: A consanguineous family with the clinical phenotype of LQTS was screened for mutations in the KVLQT1 gene. Complementary RNAs for injection into Xenopus oocytes were prepared, and currents were recorded with the double microelectrode technique. A homozygous missense mutation, leading to an alanine-to- threonine substitution at the beginning of the pore domain of the KVLQT1 channel, was found in the proband, a 9-year-old boy with normal hearing, a prolonged QT interval, and syncopal episodes during physical exercise. The parents of the proband were heterozygous for the mutation and had a normal QT interval. The functional evaluation of the mutant channel activity showed reduction in total current, a hyperpolarizing shift in activation, and a faster activation rate consistent with a mild mutation likely to require homozygosity to manifest the phenotype. CONCLUSIONS: These findings provide the first evidence for a recessive form of the Romano-Ward long-QT syndrome and indicate that homozygous mutations on KVLQT1 do not invariably produce the Jervell and Lange-Nielsen syndrome. The implications of this observation prompt a reconsideration of the penetrance of different mutations responsible for LQTS and suggest that mild mutations in LQTS genes may be present among the general population and may predispose to drug-induced ventricular arrhythmias.
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Authors | S G Priori, P J Schwartz, C Napolitano, L Bianchi, A Dennis, M De Fusco, A M Brown, G Casari |
Journal | Circulation
(Circulation)
Vol. 97
Issue 24
Pg. 2420-5
(Jun 23 1998)
ISSN: 0009-7322 [Print] United States |
PMID | 9641694
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Child
- Consanguinity
- Female
- Genes, Recessive
- Homozygote
- Humans
- Long QT Syndrome
(genetics)
- Male
- Pedigree
- Point Mutation
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