title: 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 theSCN5Agene and c.28730C>T in theTTNgene.Conclusions. Compound heterozygous variants in theSCN5Agene 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 theSCN5Agene were the most possible disease-causing variants in this family.
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand; Excelence Center for Genomic Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chuphong
authors.initials: C
authors.lastname: Thongnak
authors.affiliation: Human Genetics Unit, Department of Pathology, Faculty of Medicine, Prince of Songkla Univerisity, Hat Yai, Songkhla, Thailand.
authors.forename: Pornprot
authors.identifier: 0000-0001-5022-5361
authors.initials: P
authors.lastname: Limprasert
authors.affiliation: Rajanagarindra Institute of Child Development, Chiang Mai, Thailand.
authors.forename: Duangkamol
authors.initials: D
authors.lastname: Tangviriyapaiboon
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Suchaya
authors.initials: S
authors.lastname: Silvilairat
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Apichaya
authors.initials: A
authors.lastname: Puangpetch
authors.affiliation: Excelence Center for Genomic Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Virology Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ekawat
authors.initials: E
authors.lastname: Pasomsub
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Chonlaphat
authors.identifier: 0000-0003-0033-5321
authors.initials: C
authors.lastname: Sukasem
authors.affiliation: Excelence Center for Genomic Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Virology Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wasun
authors.identifier: 0000-0002-8821-3945
authors.initials: W
authors.lastname: Chantratita
mesh_terms: D000328:Adult; D002648:Child; D064211:Connectin / Q000235:genetics; D059472:Exome; D005260:Female; D006327:Heart Block / Q000151:congenital* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree
chemical_list: D064211:Connectin; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; C577285:TTN protein, human