title: Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia.
abstract: We sought to explore the genotype-phenotype of Jervell and Lange-Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Six families with at least one JLNS-affected member attended our clinic between 2011 and 2013. Retrospective and prospective clinical data were collected and genetic investigation was performed. Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients. The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T. All living JLNS patients except one had a QTc of >500 ms and a history of recurrent syncope. β-Blockers abolished the cardiac-related events in all patients except two siblings with homozygous Ile567Thr mutation. Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients. Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias. Mutations detected in this study will be advantageous in tribe and region-specific cascade screening of LQTS in Saudi Arabia.
authors.affiliation: Department of Genetic Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; Princess Al Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: J Y
authors.initials: JY
authors.lastname: Al-Aama
authors.forename: S
authors.initials: S
authors.lastname: Al-Ghamdi
authors.forename: A Y
authors.initials: AY
authors.lastname: Bdier
authors.forename: A
authors.initials: A
authors.lastname: AlQarawi
authors.forename: O A
authors.initials: OA
authors.lastname: Jiman
authors.forename: N
authors.initials: N
authors.lastname: Al-Aama
authors.forename: J
authors.initials: J
authors.lastname: Al-Aata
authors.forename: A A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Z A
authors.initials: ZA
authors.lastname: Bhuiyan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D003241:Consanguinity; D005838:Genotype; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012529:Saudi Arabia; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D000319:Adrenergic beta-Antagonists; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: JLNS; LQTS; consanguinity; phenotype-genotype