Sodium Channelopathy Underlying Familial Sick Sinus Syndrome With Early Onset and Predominantly Male Characteristics
| Autor: | Hirokazu Yamamoto, Naokata Sumitomo, Satoki Fukae, Akihiko Nogami, Naomasa Makita, Yasushi Oginosawa, Hideki Motomura, Taisuke Ishikawa, Taku Machida, Takeru Makiyama, Ichiro Watanabe, Masaki Kohno, Yukiomi Tsuji, Daniel Toshio Harrell, Koji Maemura, Keisuke Abe, Haruhiko Abe, Taichi Watabe, Kimie Ohkubo |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Proband congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Candidate gene Adolescent DNA Mutational Analysis Sick sinus syndrome Compound heterozygosity NAV1.5 Voltage-Gated Sodium Channel Young Adult Age Distribution Rare Diseases Japan Channelopathy Physiology (medical) Internal medicine gender Humans Medicine Genetic Predisposition to Disease Genetic Testing cardiovascular diseases Age of Onset Sex Distribution SCN5A Brugada syndrome business.industry Incidence medicine.disease Pedigree SSS Endocrinology Child Preschool Channelopathies Female mutation Age of onset Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation: Arrhythmia and Electrophysiology. 7:511-517 |
| ISSN: | 1941-3084 1941-3149 |
| Popis: | Background-Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in a familial form with a variable mode of inheritance. Despite the identifcation of causative genes, including cardiac Na channel (SCN5A), the pathogenesis and molecular epidemiology of familial SSS remain undetermined primarily because of its rarity. Methods and Results-We genetically screened 48 members of 15 SSS families for mutations in several candidate genes and determined the functional properties of mutant Na channels using whole-cell patch clamping. We identifed 6 SCN5A mutations including a compound heterozygous mutation. Heterologously expressed mutant Na channels showed loss-of-function properties of reduced or no Na current density in conjunction with gating modulations. Among 19 family members with SCN5A mutations, QT prolongation and Brugada syndrome were associated in 4 and 2 individuals, respectively. Age of onset in probands carrying SCN5A mutations was signifcantly less (mean±SE, 12.4±4.6 years; n=5) than in SCN5A-negative probands (47.0±4.6 years; n=10; P Circulation: Arrhythmia and Electrophysiology, 7(3), pp.511-517; 2014 |
| Databáze: | OpenAIRE |
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