Genomic Organization of the KCNQ1 K + Channel Gene and Identification of C-Terminal Mutations in the Long-QT Syndrome
| Autor: | Ricardo Pesce, Philippe Coumel, Maria Shkolnikova, Ketty Schwartz, Nicolas Vignier, Claire Donger, Pascale Guicheney, Pascale Richard, Nathalie Neyroud, Philippe Chevalier, Bernard Hainque, L. Demay, Isabelle Denjoy |
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| Přispěvatelé: | CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de cardiologie, Hôpital Est -Lyon, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Myologie |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Male
Potassium Channels MESH: Mutation Physiology Long QT syndrome 030204 cardiovascular system & hematology MESH: Base Sequence medicine.disease_cause Sudden death MESH: KCNQ1 Potassium Channel 03 medical and health sciences Exon 0302 clinical medicine [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system medicine Humans Missense mutation KvLQT1 030304 developmental biology Genetics 0303 health sciences Mutation MESH: Humans Base Sequence KCNQ Potassium Channels biology MESH: Long QT Syndrome Single-strand conformation polymorphism MESH: Potassium Channels medicine.disease MESH: Male 3. Good health Long QT Syndrome genomic DNA Potassium Channels Voltage-Gated KCNQ1 Potassium Channel biology.protein MESH: KCNQ Potassium Channels Female MESH: Microsatellite Repeats Cardiology and Cardiovascular Medicine MESH: Female MESH: Potassium Channels Voltage-Gated Microsatellite Repeats |
| Zdroj: | Circulation Research Circulation Research, American Heart Association, 1999, 84 (3), pp.290-297. ⟨10.1161/01.res.84.3.290⟩ Circulation Research, 1999, 84 (3), pp.290-297. ⟨10.1161/01.res.84.3.290⟩ ResearcherID |
| ISSN: | 0009-7330 1524-4571 |
| DOI: | 10.1161/01.res.84.3.290⟩ |
| Popis: | 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 α 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. |
| Databáze: | OpenAIRE |
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