KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome

KVLQT1, the gene encoding the alpha-subunit of a cardiac potassium channel, is the most common cause of the dominant form of long-QT syndrome (LQT1-type), the Romano-Ward syndrome (RWS). The overall phenotype of RWS is characterized by a prolonged QT interval on the ECG and cardiac ventricular arrhy...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1997-11, Vol.96 (9), p.2778-2781
Main Authors: DONGER, C, DENJOY, I, BERTHET, M, NEYROUD, N, CRUAUD, C, BENNACEUR, M, CHIVORET, G, SCHWARTZ, K, COUMEL, P, GUICHENEY, P
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Cardiac dysrhythmias
Cardiology and cardiovascular system
Cardiology. Vascular system
Electrocardiography
Female
Heart
Human health and pathology
Humans
KCNQ Potassium Channels
KCNQ1 Potassium Channel
Life Sciences
Long QT Syndrome
Long QT Syndrome - genetics
Male
Medical sciences
Mutation
Potassium Channels
Potassium Channels - genetics
Potassium Channels, Voltage-Gated
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Summary:KVLQT1, the gene encoding the alpha-subunit of a cardiac potassium channel, is the most common cause of the dominant form of long-QT syndrome (LQT1-type), the Romano-Ward syndrome (RWS). The overall phenotype of RWS is characterized by a prolonged QT interval on the ECG and cardiac ventricular arrhythmias leading to recurrent syncopes and sudden death. However, there is considerable variability in the clinical presentation, and potential severity is often difficult to evaluate. To analyze the relationship between phenotypes and underlying defects in KVLQT1, we investigated mutations in this gene in 20 RWS families originating from France. By PCR-SSCP analysis, 16 missense mutations were identified in KVLQT1, 11 of them being novel. Fifteen mutations, localized in the transmembrane domains S2-S3, S4-S5, P, and S6, were associated with a high percentage of symptomatic carriers (55 of 95, or 58%) and sudden deaths (23 of 95, or 24%). In contrast, a missense mutation, Arg555Cys, identified in the C-terminal domain in 3 families, was associated with a significantly less pronounced QT prolongation (459+/-33 ms, n=41, versus 480+/-32 ms, n=70, P=.0012), and significantly lower percentages of symptomatic carriers (7 of 44, or 16%, P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.96.9.2778