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


Temel Ş. G. , Toksoy G. , Uysal F., Bostan O., Evke E., Uyguner Z. O. , ...Daha Fazla

European Human Genetics Conference 2015, Glasgow, İngiltere, 6 - 09 Haziran 2015, cilt.1, no.1, ss.122-123

  • Cilt numarası: 1
  • Basıldığı Şehir: Glasgow
  • Basıldığı Ülke: İngiltere
  • Sayfa Sayıları: ss.122-123

Özet

Long QT syndrome is one of the most common congenital cardiac ion channel

disorder that the morbidity and mortality rate can be decreased by an

early diagnosis and proper treatment. Cardiac repolarization abnormality

that is characterized by prolonged OT interval and propensity for ventricular

tachycardia of the torsades de pointes type are characteristics of the

disease. This syndrome represents high risk for presyncope, syncope, cardiac

arrest and sudden death. Jervell and Lange-Nielsen syndrome (JLNS)

is recessive form of long QT syndromes with additional 􀏐inding of profound

sensorineural hearing loss. JLNS has been shown to occur due to homozygous

and compound heterozygous mutations in KCNQ1 or KCNE1. Pathogenic

mutations in the KCNQ1 gene were detected in all our JLNS cases. Index

cases of 3 families were 2 month yr, 3.5 yr old female and 3-yr old male

who visited the hospital due to intrauterine bradicardia, recurrent seizures/

syncope, cardiac murmur, respectively and had all congenital sensorineural

deafness. Their electrocardiograms revealed a markedly prolonged QT

interval. The sequence analysis of the probands revealed the presence of

compound 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 on

the 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 is

long she had intact hearing. β-blocker therapy was initiated to all affected

ones. Asymptomatic heterozygous family members were taken to a clinical

follow up. Clinical and moleular 􀏐indings will be discussed to further enlighten

the genotype-phenotype association.