Exome Sequencing Identifies Compound Heterozygous Mutations inSCN5AAssociated with Congenital Complete Heart Block in the Thai Population

Abstract

Background. Congenital heart block is characterized by blockage of electrical impulses from the atrioventricular node (AV node) to the ventricles. This blockage can be caused by ion channel impairment that is the result of genetic variation. This study aimed to investigate the possible causative variants in a Thai family with complete heart block by using whole exome sequencing. Methods. Genomic DNA was collected from a family consisting of five family members in three generations in which one of three children in generation III had complete heart block. Whole exome sequencing was performed on one complete heart block affected child and one unaffected sibling. Bioinformatics was used to identify annotated and filtered variants. Candidate variants were validated and the segregation analysis of other family members was performed. Results. This study identified compound heterozygous variants, c.101G>A and c.3832G>A, in the SCN5A gene and c.28730C>T in the TTN gene. Conclusions. Compound heterozygous variants in the SCN5A gene were found in the complete heart block affected child but these two variants were found only in the this affected sibling and were not found in other unaffected family members. Hence, these variants in the SCN5A gene were the most possible disease-causing variants in this family.

Whole-Exome Sequencing Identifies One De Novo Variant in theFGD6Gene in a Thai Family with Autism Spectrum Disorder

“…Additionally, since one autism-affected child, 2.III-2, of family number 2 had heart block along with ASD, a cause of this heart defect was explored in our previous publication. The previous result revealed that autism and heart block in this family are coincidental, not likely to be Timothy syndrome [ 18 ].…”

“…The family number 2 had three generations, of whom four out of seven members were available for DNA study, an unaffected grandmother (2.I-2), an unaffected mother (2.II-2), and two children with autism (2.III-2 and 2.III-3). The proband of the family number 2 (2.III-2) had also been included in another study [ 18 ]. The clinical information of both families is shown in Supplementary 1 .…”

Matrix metalloproteinase 1 1 G/2 G gene polymorphism is associated with acquired atrioventricular block via linking a higher serum protein level

“…Increasing evidence suggests that gene mutations and dysfunction of the conduction system during heart development may result in familial AVB [9][10][11][12] . However, only a few data are available regarding the pathophysiology of acquired AVB.…”

“…Progressive idiopathic fibrosis related to an aging process of the cardiac skeleton is the most common cause of chronic acquired AVB 2,[4][5][6][7][8] . It is generally accepted that familial and inherited AVB are caused by gene mutations and dysfunction of the conduction system during heart development [9][10][11][12] . In contrast, the pathophysiological mechanism of acquired AVB is currently unclear.…”

Association study of new polymorphisms with sudden cardiac death in men

“…Ген SCN5A (sodium voltage-gated channel alpha subunit 5, 3p22.2) кодирует α-субъединицу натриевого канала. Дефекты гена связаны с развитием синдрома удлиненного интервала QT (LQT3) [17].…”