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J u l y 2 3 - 2 4 , 2 0 1 8 | R o m e , I t a l y
allied
academies
Joint Event on
Cardiology Congress 2018 & Microbe Infection 2018
Biomedical Research
|
ISSN: 0976-1683
|
Volume 29
2
nd
World Congress on
CARDIOLOGY
MICROBIOLOGY AND MICROBIAL INFECTION
&
39
th
Annual Congress on
Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C1-003
NOVEL COMPOUND HETEROZYGOUS MUTATIONS OF
KCNQ1
IN LONG
QT SYNDROME WITH FAMILIAL HISTORY OF UNEXPLAINED SUDDEN
DEATH: IDENTIFIED BY ANALYSIS OF WHOLE EXOME SEQUENCING AND
PREDISPOSING GENES
Ting Zhao
1
, Yubi Lin
1
, Zifeng Huang
2
and
Hongyun Lu
1
1
The Fifth Affiliated Hospital of Sun Yat-Sen University, China
2
Jinan University, China
Aim & Objective:
This study aimed to identify the pathogenic mutation in a Chinese family with long QT syndrome (LQTs) and
unexplained sudden death (USD).
Methods & Results:
Whole exome sequencing was conducted for the proband. The genetic data was screened using the 1000
genomes project and SNP database (PubMed), and the identified mutations were assessed for predicted pathogenicity using the
SIFT and polyphen-2 algorithms. We identified the compound heterozygous mutations in the
KCNQ1
gene at c. G527A (p. W176X)
and c. G1765A (p. G589S) predicted as damaging. The
in-silico
analysis showed that when compared to the characteristics of
mRNA and protein of wild-type
KCNQ1
, the mRNA of c. G527A mutation was significantly different in the centroid secondary
structure; the subunit coded by W176X would lose the transmembrane domains S3-S6 and helices A-D; the protein secondary
structure of G598S was slightly shortened in helix structure; the protein physics-chemical parameters of W176X and G589S
significantly and slightly changed, respectively.
Conclusions:
The compound heterozygous mutations of W176X and G589S coexisting in
KCNQ1
gene of homologous
chromosomes, resulting in more severe phenotype, are the likely pathogenic and genetic risks of LQTs and USD in this Chinese
family.