title: Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.
abstract: 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.
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Hopital CardioVasculaire et Pneumologique L Pradel, Bron, France, and Unidad de neonatología Servicio de pediatría, Hospital Universitario Río Hortega, Valladolid, Spain. gilles.millat@chu-lyon.fr
authors.forename: G
authors.initials: G
authors.lastname: Millat
authors.forename: P
authors.initials: P
authors.lastname: Chevalier
authors.forename: L
authors.initials: L
authors.lastname: Restier-Miron
authors.forename: A
authors.initials: A
authors.lastname: Da Costa
authors.forename: P
authors.initials: P
authors.lastname: Bouvagnet
authors.forename: B
authors.initials: B
authors.lastname: Kugener
authors.forename: L
authors.initials: L
authors.lastname: Fayol
authors.forename: C
authors.initials: C
authors.lastname: Gonzàlez Armengod
authors.forename: B
authors.initials: B
authors.lastname: Oddou
authors.forename: V
authors.initials: V
authors.lastname: Chanavat
authors.forename: E
authors.initials: E
authors.lastname: Froidefond
authors.forename: R
authors.initials: R
authors.lastname: Perraudin
authors.forename: R
authors.initials: R
authors.lastname: Rousson
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000235:genetics*; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels