Mutation screening of KCNQ1 and KCNE1 genes in Iranian patients with Jervell and lange Nielsen syndrome

Objective: Jervell and Lange-Nielsen syndrome (JLNS), the long-QT syndrome (LQTS) variant, is associated withprofound sensorineural deafness, syncope, sudden death, and have an autosomal recessive inheritance. The KCNQ1 andKCNE1 proteins co-assemble in a potassium channel, responsible for the cardiac IKs current which is involved inrepolarization of the ventricular action potential. Mutations in KCNQ1 gene or the KCNE1 genes have been identified inJLNS and in autosomal-dominant LQTS as well. Some heterozygous carriers of JLNS mutations in either gene are onlyoccasionally symptomatic, although they may have prolonged QTc. Our objective was to perform mutational analysis inKCNQ1 and KCNE1 genes from a clinically diagnosed Iranian population with JLNS.Methods: Fourteen Iranian patients with clinical evidence of JLNS were investigated. Mutational screening in KCNQ1 andKCNE1 genes was performed by polymerase chain reaction (PCR) followed by direct Sanger sequencing.Results: We identified two novel mutations in KCNQ1 gene, including c.1642delG, a novel single nucleotide deletionwhich was identified in a 6-year-old female patient with history of syncope and congenital sensorineural deafness. Herparents were carrier of the same mutation. Another novel mutation, c.1463delG, was identified in a 5-year-old femalepatient who had deafness and QTC prolongation. Heterozygous mutations of KCNQ1 were identified in both parents. Bothof the single nucleotide deletions represent new JLNS-associated mutations in KVLQT1 and have disadvantageous effectson the KVLQT1 potassium channel. These genetic variations lead to frameshift mutation and premature termination of Cterminuswith truncation of the postulated assembly domain of the KVLQT1 protein. A common single nucleotidepolymorphism (SNP), c.112G> A (p. Gly38Ser) was also found in KCNE1 in seven probands.Conclusions: The results revealed novel single nucleotide deletion mutations in C-terminus of KCNQ1 that can predisposeto JLNS.

کلیدواژه ها:

KCNQ1 ، KCNE1 ، the Jervell and Lange-Nielsen syndrome (JLNS) ، genetic mutation