Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome

Qiuyun Chen, Danmei Zhang, Robert L. Gingell, Arthur J. Moss, Carlo Napolitano, Silvia G. Priori, Peter J. Schwartz, Eileen Kehoe, Jennifer L. Robinson, Eric Schulze-Bahr, Qing Wang, Jeffrey Towbin

Research output: Contribution to journalArticle

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Abstract

Background - Long-QT (LQT) syndrome is a cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported. Heterozygous mutations in 3 potassium channel genes, KVLQT1, KCNE1 (minK), and HERG, and the cardiac sodium channel gene SCN5A cause autosomal dominant LQT. Autosomal recessive LQT, which is associated with deafness, has been found to occur with homozygous mutations in KVLQT1 and KCNE1 in JLNS families in which QTc prolongation was inherited as a dominant trait. Methods and Results - An Amish family with clinical evidence of JLNS was analyzed for mutations by use of single-strand conformation polymorphism and DNA sequencing analyses for mutations in all known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment of KVLQT1 was identified in affected members of this Amish family in which both QTc prolongation and deafness were inherited as recessive traits. This deletion represents a new JLNS-associated mutation in KVLQT1 and has deleterious effects on the KVLQT1 potassium channel, causing a frameshift and the truncation of the KVLQT1 protein. In contrast to previous reports in which LQT was inherited as a clear dominant trait, 2 parents in the JLNS family described here have normal QTc intervals (0.43 and 0.44 seconds, respectively). Conclusions - A novel homozygous KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait.

Original languageEnglish (US)
Pages (from-to)1344-1347
Number of pages4
JournalCirculation
Volume99
Issue number10
DOIs
StatePublished - Mar 16 1999
Externally publishedYes

Fingerprint

Jervell-Lange Nielsen Syndrome
Amish
Mutation
Deafness
Potassium Channels
KCNQ1 Potassium Channel
Romano-Ward Syndrome
Genes
Mink
Torsades de Pointes
Long QT Syndrome
Sodium Channels
Syncope
Sudden Death
DNA Sequence Analysis
Cardiac Arrhythmias
Seizures
Parents

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Chen, Q., Zhang, D., Gingell, R. L., Moss, A. J., Napolitano, C., Priori, S. G., ... Towbin, J. (1999). Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome. Circulation, 99(10), 1344-1347. https://doi.org/10.1161/01.CIR.99.10.1344

Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome. / Chen, Qiuyun; Zhang, Danmei; Gingell, Robert L.; Moss, Arthur J.; Napolitano, Carlo; Priori, Silvia G.; Schwartz, Peter J.; Kehoe, Eileen; Robinson, Jennifer L.; Schulze-Bahr, Eric; Wang, Qing; Towbin, Jeffrey.

In: Circulation, Vol. 99, No. 10, 16.03.1999, p. 1344-1347.

Research output: Contribution to journalArticle

Chen, Q, Zhang, D, Gingell, RL, Moss, AJ, Napolitano, C, Priori, SG, Schwartz, PJ, Kehoe, E, Robinson, JL, Schulze-Bahr, E, Wang, Q & Towbin, J 1999, 'Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome', Circulation, vol. 99, no. 10, pp. 1344-1347. https://doi.org/10.1161/01.CIR.99.10.1344
Chen Q, Zhang D, Gingell RL, Moss AJ, Napolitano C, Priori SG et al. Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome. Circulation. 1999 Mar 16;99(10):1344-1347. https://doi.org/10.1161/01.CIR.99.10.1344
Chen, Qiuyun ; Zhang, Danmei ; Gingell, Robert L. ; Moss, Arthur J. ; Napolitano, Carlo ; Priori, Silvia G. ; Schwartz, Peter J. ; Kehoe, Eileen ; Robinson, Jennifer L. ; Schulze-Bahr, Eric ; Wang, Qing ; Towbin, Jeffrey. / Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome. In: Circulation. 1999 ; Vol. 99, No. 10. pp. 1344-1347.
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abstract = "Background - Long-QT (LQT) syndrome is a cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported. Heterozygous mutations in 3 potassium channel genes, KVLQT1, KCNE1 (minK), and HERG, and the cardiac sodium channel gene SCN5A cause autosomal dominant LQT. Autosomal recessive LQT, which is associated with deafness, has been found to occur with homozygous mutations in KVLQT1 and KCNE1 in JLNS families in which QTc prolongation was inherited as a dominant trait. Methods and Results - An Amish family with clinical evidence of JLNS was analyzed for mutations by use of single-strand conformation polymorphism and DNA sequencing analyses for mutations in all known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment of KVLQT1 was identified in affected members of this Amish family in which both QTc prolongation and deafness were inherited as recessive traits. This deletion represents a new JLNS-associated mutation in KVLQT1 and has deleterious effects on the KVLQT1 potassium channel, causing a frameshift and the truncation of the KVLQT1 protein. In contrast to previous reports in which LQT was inherited as a clear dominant trait, 2 parents in the JLNS family described here have normal QTc intervals (0.43 and 0.44 seconds, respectively). Conclusions - A novel homozygous KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait.",
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AU - Chen, Qiuyun

AU - Zhang, Danmei

AU - Gingell, Robert L.

AU - Moss, Arthur J.

AU - Napolitano, Carlo

AU - Priori, Silvia G.

AU - Schwartz, Peter J.

AU - Kehoe, Eileen

AU - Robinson, Jennifer L.

AU - Schulze-Bahr, Eric

AU - Wang, Qing

AU - Towbin, Jeffrey

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Y1 - 1999/3/16

N2 - Background - Long-QT (LQT) syndrome is a cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported. Heterozygous mutations in 3 potassium channel genes, KVLQT1, KCNE1 (minK), and HERG, and the cardiac sodium channel gene SCN5A cause autosomal dominant LQT. Autosomal recessive LQT, which is associated with deafness, has been found to occur with homozygous mutations in KVLQT1 and KCNE1 in JLNS families in which QTc prolongation was inherited as a dominant trait. Methods and Results - An Amish family with clinical evidence of JLNS was analyzed for mutations by use of single-strand conformation polymorphism and DNA sequencing analyses for mutations in all known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment of KVLQT1 was identified in affected members of this Amish family in which both QTc prolongation and deafness were inherited as recessive traits. This deletion represents a new JLNS-associated mutation in KVLQT1 and has deleterious effects on the KVLQT1 potassium channel, causing a frameshift and the truncation of the KVLQT1 protein. In contrast to previous reports in which LQT was inherited as a clear dominant trait, 2 parents in the JLNS family described here have normal QTc intervals (0.43 and 0.44 seconds, respectively). Conclusions - A novel homozygous KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait.

AB - Background - Long-QT (LQT) syndrome is a cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported. Heterozygous mutations in 3 potassium channel genes, KVLQT1, KCNE1 (minK), and HERG, and the cardiac sodium channel gene SCN5A cause autosomal dominant LQT. Autosomal recessive LQT, which is associated with deafness, has been found to occur with homozygous mutations in KVLQT1 and KCNE1 in JLNS families in which QTc prolongation was inherited as a dominant trait. Methods and Results - An Amish family with clinical evidence of JLNS was analyzed for mutations by use of single-strand conformation polymorphism and DNA sequencing analyses for mutations in all known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment of KVLQT1 was identified in affected members of this Amish family in which both QTc prolongation and deafness were inherited as recessive traits. This deletion represents a new JLNS-associated mutation in KVLQT1 and has deleterious effects on the KVLQT1 potassium channel, causing a frameshift and the truncation of the KVLQT1 protein. In contrast to previous reports in which LQT was inherited as a clear dominant trait, 2 parents in the JLNS family described here have normal QTc intervals (0.43 and 0.44 seconds, respectively). Conclusions - A novel homozygous KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as an autosomal recessive trait.

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