Türkgenç, BurcuToksoy, GüvenEvke, ElifUyguner, OyaYakıciğer, CengizKayserili, Hülya2023-09-052023-09-052017-10-01Uysal, F. vd. (2017). ''Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: Case reports''. BMC Medical Genetics, 18(1).1471-2350https://doi.org/10.1186/s12881-017-0474-8https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644177/http://hdl.handle.net/11452/33748Background: Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients. Case presentations: Three patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively; moreover all three patients had congenital sensorineural hearing-loss. Their electrocardiograms showed markedly prolonged QT interval. Implantable defibrillator was implanted and left cardiac sympathetic denervation was performed due to the progressive disease in case 1. She had countless ventricular fibrillation and appropriate shock while using an implantable defibrillator. The DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A (p.Arg243His) missense mutation in case1. Further targeted next generation sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T > G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr) variant in NKX2-5 gene in the same patient. Additional gene alterations in RYR2 and NKX2-5 genes were thought to be responsible for progressive and malignant course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1 genes, a compound heterozygosity for two mutations had been detected in KCNQ1 gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln) mutation in KCNQ1 gene in case 3. beta-blocker therapy was initiated to all the index subjects. Conclusions: Three families of JLNS who presented with long QT and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1 gene were presented in this report. It was emphasized that broad targeted cardiac panels may be useful to predict the outcome especially in patients with unexplained phenotype-genotype correlation. Clinical presentations and molecular findings will be discussed further to clarify the phenotype genotype associations.eninfo:eu-repo/semantics/openAccessGenetics & heredityJervell lange nielsen syndromeDeafnessHomozygous or compound heterozygous mutationsCase reportLong-qt syndromeMissense mutationKcnq1 geneKvlqt1PrevalencePhenotypeSpectrumTherapyChannelKcne1Adrenergic beta antagonistsChild, preschoolElectrocardiographyFemaleHearing loss, sensorineuralHeterozygoteHigh throughput nucleotide sequencingHomeobox protein Nkx-2.5HomozygoteHumansInfantJervell lange nielsen syndromeKCNQ1 potassium channelMalePedigreePolymorphismPotassium channelsRyanodine receptor calcium release channelSequence AnalysisDNATurkeyVoltage-gatedSingle nucleotideArticle0004132211000012-s2.0-8503149977618129037160Genetics & heredityPotassium Channels; Jervell-Lange Nielsen Syndrome; Torsade Des PointesHomeobox protein Nkx-2.5Potassium channel KCNE1Potassium channel KCNQ1PropranololRyanodine receptor 2Beta adrenergic receptor blocking agentHomeobox protein Nkx-2.5KCNE1 protein, humanKCNQ1 protein, humanNKX2-5 protein, humanPotassium channel KCNQ1Ryanodine receptorRyR2 protein, humanVoltage gated potassium channelArticleBradycardiaBrainstem evoked response audiometryCase reportChildClinical articleConsanguineous marriageDisease associationDrug resistant epilepsyEvoked response audiometryFemaleFollow upGene frequencyGene mutationGenetic analysisGenetic variabilityHearing impairmentHeterozygosityHomozygosityHospitalizationHumanInfantIntensive care unitJervell and Lange nielsen syndromeKCNE1 geneKCNQ1 geneMaleMissense mutationNKX2 5 genePerinatal periodPhenotypePhysical examinationPreschool childQT intervalQT prolongationQTc prolongationRYR2 geneSingle nucleotide polymorphismSplice site mutationSympathectomyTachypneaDNA sequenceElectrocardiographyGeneticsHearing LossSensorineuralHeterozygoteHigh throughput sequencingHomozygoteJervell lange nielsen syndromePedigreeProceduresSingle nucleotide polymorphismTurkey