Genomic Organization of the KCNQ1 K + Channel Gene and Identification of C-Terminal Mutations in the Long-QT Syndrome - Sorbonne Université Access content directly
Journal Articles Circulation Research Year : 1999

Genomic Organization of the KCNQ1 K + Channel Gene and Identification of C-Terminal Mutations in the Long-QT Syndrome

Nathalie Neyroud
Pascale Richard
Claire Donger
  • Function : Author
Isabelle Denjoy
Laurence Demay
  • Function : Author
  • PersonId : 895073
Maria Shkolnikova
  • Function : Author
Ricardo Pesce
  • Function : Author
Philippe Coumel
  • Function : Author

Abstract

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.

Dates and versions

hal-02330607 , version 1 (24-10-2019)

Identifiers

Cite

Nathalie Neyroud, Pascale Richard, Nicolas Vignier, Claire Donger, Isabelle Denjoy, et al.. Genomic Organization of the KCNQ1 K + Channel Gene and Identification of C-Terminal Mutations in the Long-QT Syndrome. Circulation Research, 1999, 84 (3), pp.290-297. ⟨10.1161/01.res.84.3.290⟩. ⟨hal-02330607⟩
26 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More