title: Jervell and Lange-Nielsen syndrome: homozygous missense mutation of KCNQ1 in a Turkish family.
abstract: Long QT syndrome is one of the most common cardiac ion channel diseases, but its morbidity and mortality rate can be lessened with an early diagnosis and proper treatment. This cardiac ventricular repolarization abnormality is characterized by a prolonged QT interval and a propensity for ventricular tachycardia (VT) of the torsades de pointes type. The long QT syndrome represents a high risk for presyncope, syncope, cardiac arrest, and sudden death. Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited form of long QT syndrome characterized by profound sensorineural deafness and prolongation of the QT interval. Findings have shown that JLNS occurs due to homozygous and compound heterozygous pathogenic variants in KCNQ1 or KCNE1. A 3.5-year-old girl presented to the hospital with recurrent syncope, seizures, and congenital sensorineural deafness. Her electrocardiogram showed a markedly prolonged QT interval, and she had a diagnosis of JLNS. The sequence analysis of the proband showed the presence of a pathogenic homozygous missense variant (c.728G>A, p.Arg243His). Heterozygous mutations of KCNQ1 were identified in her mother, father, and sister, demonstrating true homozygosity. Even with high-dose beta-blocker therapy, the patient had two VT attacks, so an implantable cardioverter defibrillator was fitted. The authors suggest early genetic diagnosis for proper management of the disease in the proband and genetic counseling for both the proband and the girl's extended family.
authors: Department of Paediatric Cardiology, Faculty of Medicine, University of Uludag, Bursa, Turkey.
authors: Ozlem
authors: O
authors: Bostan
authors: Şehime G
authors: ŞG
authors: Temel
authors: Hakan
authors: H
authors: Cangül
authors: Caroline N S
authors: CN
authors: Archer
authors: Ergun
authors: E
authors: Çil
mesh_terms: D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree; D014421:Turkey
chemical_list: D051657:KCNQ1 Potassium Channel; D004247:DNA
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