title: LQTS in Northern BC: homozygosity for KCNQ1 V205M presents with a more severe cardiac phenotype but with minimal impact on auditory function.
abstract: Long QT syndrome (LQTS), a rare congenital cardiac condition associated with life-threatening ventricular arrhythmias is characterized by a prolonged QT interval on electrocardiograph corrected for heart rate [corrected QT (QTc)]. LQTS has been historically categorized into the autosomal dominant Romano-Ward syndrome (RWS) and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS). JLNS is associated with prelingual sensorineural deafness. Both types of LQTS can be caused by mutations in channel genes (e.g. KCNQ1) responsible for potassium homeostasis in cardiac myocytes and cochlea. Autosomal dominant mutations often cause the RWS phenotype and homozygous or compound heterozygous mutations contribute to JLNS. Two First Nations communities in northern British Columbia are affected disproportionately with LQTS largely due to the V205M mutation in KCNQ1, however, the pathology and phenotypic expression for those V205M homozygous has been unknown. Here, we show that four V205M homozygous individuals have a significantly higher 'peak' QTc, and a more severe cardiac phenotype compared with 41 V205M heterozygous carriers and 57 first to third degree relatives without mutations. Given the lack of prelingual deafness the homozygous V205M LQTS patients present with a phenotype more typical of RWS than JLNS.
authors.affiliation: Department of Medical Genetics and the Island Medical program, University of British Columbia, Victoria, British Columbia, Canada.
authors.forename: H A
authors.initials: HA
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: McIntosh
authors.forename: B
authors.initials: B
authors.lastname: Whittome
authors.forename: S
authors.initials: S
authors.lastname: Asuri
authors.forename: B
authors.initials: B
authors.lastname: Casey
authors.forename: C
authors.initials: C
authors.lastname: Kerr
authors.forename: A
authors.initials: A
authors.lastname: Tang
authors.forename: L T
authors.initials: LT
authors.lastname: Arbour
mesh_terms: D001955:British Columbia; D003638:Deafness / Q000209:etiology / Q000473:pathology*; D004562:Electrocardiography; D006720:Homozygote; D006801:Humans; D007198:Indians, North American; D029593:Jervell-Lange Nielsen Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D029597:Romano-Ward Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: JLNS; RWS; V205M; hearing loss; long QT syndrome