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Identification of a novel KCNQ1 mutation in a large Saudi family with long QT syndrome: clinical consequences and preventive implications
Author(s) -
Shinwari ZMA,
AlHazzani A,
Dzimiri N,
Tulbah S,
Mallawi Y,
AlFayyadh M,
AlHassnan ZN
Publication year - 2013
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2012.01914.x
Subject(s) - long qt syndrome , proband , qt interval , medicine , mutation , genetic testing , genetic counseling , genetics , gene , biology
Congenital long QT syndrome ( LQTS ) is an inherited potentially fatal arrhythmogenic disorder that is characterized by prolonged corrected QT ( QTc ) interval. Mutations in three genes ( KCNQ1 , KCNH2 , and SCN5A ) account for the majority of the cases. However, 10 other genes are now known to be implicated in LQTS . In this work, we describe the clinical and molecular analysis in a large Saudi family with LQTS . Screening KCNQ1 , KCNH2 , and SCN5A genes in the proband, who presented with syncope, led to the identification of a heterozygous mutation ( p.H258P ) in KCNQ1 . An extended clinical and genetic screening of the family identified 11 other members who were carriers for this mutation. All identified carriers had prolonged QTc intervals; yet, only two were symptomatic. Screening the family members for three LQTS modifiers (rs4657139 and rs16847548 in NOS1AP and KCNE1 ‐ D85N ) did not reveal a correlation with symptoms or QTc intervals. The electrocardiographic and molecular analysis stratified seven carriers at high risk of a cardiac event as they had a QTc of ≥500 ms and were carriers of a KCNQ1 mutation. Our work illustrates the importance of extended family screening in LQTS to identify silent carriers and hence adopt the most appropriate therapeutic and preventive intervention.