Homozygous and Compound Hetrozygous Mutation in 3 Turkish Family with Jervell and Lange-Nielsen Syndrome

Abstract

Long QT syndrome is one of the most common congenital cardiac ion channeldisorder that the morbidity and mortality rate can be decreased by anearly diagnosis and proper treatment. Cardiac repolarization abnormalitythat is characterized by prolonged OT interval and propensity for ventriculartachycardia of the torsades de pointes type are characteristics of thedisease. This syndrome represents high risk for presyncope, syncope, cardiacarrest and sudden death. Jervell and Lange-Nielsen syndrome (JLNS)is recessive form of long QT syndromes with additional ����inding of profoundsensorineural hearing loss. JLNS has been shown to occur due to homozygousand compound heterozygous mutations in KCNQ1 or KCNE1. Pathogenicmutations in the KCNQ1 gene were detected in all our JLNS cases. Indexcases of 3 families were 2 month yr, 3.5 yr old female and 3-yr old malewho visited the hospital due to intrauterine bradicardia, recurrent seizures/syncope, cardiac murmur, respectively and had all congenital sensorineuraldeafness. Their electrocardiograms revealed a markedly prolonged QTinterval. The sequence analysis of the probands revealed the presence ofcompound heterozygous mutation ([(c.477+1G>A) + (c.520C>T, p.R174C)]and homozygous missence mutations (c.728 G>A, p. R243H), (1097G>A,p.R366Q), respectively. Heterozygous mutation in KCNQ1 was identi����ied onthe maternal, paternal and sibling sides. Homozygous mutation was identi-����ied in 3-yr old male’s sister and cousin also. Interestingly even if her QT islong she had intact hearing. β-blocker therapy was initiated to all affectedones. Asymptomatic heterozygous family members were taken to a clinicalfollow up. Clinical and moleular ����indings will be discussed to further enlightenthe genotype-phenotype association.