Molecular Basis of the Long-QT Syndrome Associated with Deafness

Splawski, Igor; Timothy, Katherine W.; Vincent, G; Atkinson, Donald L.; Keating, Mark T.

doi:10.1056/nejm199705293362204

Cited by 317 publications

(151 citation statements)

References 22 publications

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“…Both homozygosity for mutations in KVLQT1, 13,14 and compound heterozygosity for mutations in KCNE1 15 have been shown to cause JLNS. KVLQT1 and KCNE1 encode ion channel subunits which assemble in stria vascularis of the inner ear and are necessary to maintain the composition of the endolymph, 14 and the absence of a hearing defect in our family and that of the other recently described recessive RWS family, 10 is probably explained by the mutations not completely abolishing channel function.…”

Section: Discussionmentioning

confidence: 99%

Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene

et al. 1999

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We describe a Swedish family with the proband and his brother suffering from severe RomanoWard syndome (RWS) associated with compound heterozygosity for two mutations in the KVLQT1 (also known as KCNQ1 and KCNA9) gene (R518X and A525T). The mutations were found to segregate as heterozygotes in the maternal and the paternal lineage, respectively. None of the heterozygotes exhibited clinical long QT syndrome (LQTS). No hearing defects were found in the proband. The data strongly indicates that the compound heterozygosity for R518X and A525T is the cause of an autosomal recessive form of RWS in this family. Our findings support the implication of a higher frequency of gene carriers than previously expected. We suggest that relatives of 'sporadic RWS' patients should be considered potential carriers, at risk of dying suddenly from drug-induced LQTS.

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Section: Discussionmentioning

confidence: 99%

Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene

et al. 1999

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“…To date, over 200 mutations have been identified in six separate ion channel genes that encode sodium channels (SCN5A, which causes LQT3) and potassium channels (KCNQ1 and KCNH2, which cause LQT1 and LQT2, respectively) or their regulatory subunits KCNE1 and KCNE2 (which cause LQT5 and LQT6, respectively) (7). Recently, a mutation on ankyrin-B, a cytosolic protein, has also been reported to cause the fourth type of LQTS known as LQT4 (8,9).…”

mentioning

confidence: 99%

Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes

Huang

Zhao

Barrane

et al. 2006

Canadian Journal of Cardiology

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“…Two JLN mutations have been reported so far, an insertion-deletion in the C-terminal domain of the protein and a 1-bp insertion, both leading to putative truncated proteins. 1,2 We evidenced a novel missense mutation in two consanguineous JLN families. It is the first mutation in the pore region of KvLQT1 which is the cause of an apparently normal phenotype at the heterozygous state, but a life-threatening JLN syndrome at the homozygous state.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 This disease is characterised by a congenital bilateral deafness, a prolonged QTc interval on the resting ECG, syncopal attacks due to ventricular tachyarrhythmias and a high risk of sudden death. 3,4 KvLQT1 encodes a potassium channel that produces in association with IsK the I Ks cardiac current involved in ventricular repolarization, 5 and plays an important role in the control of endolymph homeostasis in the inner ear.…”

Section: Introductionmentioning

confidence: 99%

Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an apparently normal phenotype in long QT syndrome

et al. 1998

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Mutations in KvLQT1, a gene encoding a potassium channel, cause both the recessive Jervell and Lange-Nielsen (JLN) syndrome and the dominant Romano-Ward (RW) syndrome. These diseases are characterised by a prolonged QT interval on the ECG, syncopes and sudden death due to cardiac arrhythmias. The JLN syndrome is also associated with a congenital bilateral deafness. We report here a novel missense mutation, W305S, in the pore region of KvLQT1 identified by PCR-SSCP analysis in two consanguineous JLN families. In contrast to several missense mutations found in the same region of KvLQT1 in RW patients which are associated with severe cardiac phenotypes, the W305S mutation is responsible for an apparently normal phenotype in heterozygous JLN carriers.

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Molecular Basis of the Long-QT Syndrome Associated with Deafness

Cited by 317 publications

References 22 publications

Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene

Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene

Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes

Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an apparently normal phenotype in long QT syndrome

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