Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome
| Autor: | Philippe Chevalier, B Kugener, E Froidefond, Robert Rousson, Patrice Bouvagnet, L Fayol, C Gonzàlez Armengod, A.G. da Costa, B Oddou, Gilles Millat, R Perraudin, Claire Rodriguez-Lafrasse, L Restier-Miron, Valérie Chanavat |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Nonsynonymous substitution congenital hereditary and neonatal diseases and abnormalities Adolescent Long QT syndrome Single-nucleotide polymorphism Polymorphism Single Nucleotide QT interval Sudden death Sodium Channels NAV1.5 Voltage-Gated Sodium Channel Cohort Studies Genetics Humans Medicine cardiovascular diseases Child Gene Genetics (clinical) Aged Aged 80 and over biology business.industry Infant Newborn Infant KCNE2 medicine.disease Penetrance Long QT Syndrome Amino Acid Substitution Potassium Channels Voltage-Gated Mutation biology.protein Female business |
| Zdroj: | Clinical Genetics. 70:214-227 |
| ISSN: | 0009-9163 |
| Popis: | Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes. |
| Databáze: | OpenAIRE |
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