title: A novel variant in TBX20 (p.D176N) identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect.
abstract: Congenital heart disease (CHD) is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect (ASD) is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 (TBX20) contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G>A (p.D176N), was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs (SIFT, Polyphen2, and MutationTaster). This mutation was also not presented in the current Single Nucleotide Polymorphism Database (dbSNP) or National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP). In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree.
authors.affiliation: Department of Cardiothoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, China; Department of Cell Biology, School of Life Sciences, Central South University, Changsha 410013, China; Center of Clinical Gene Diagnosis and Therapy, the State Key Laboratory of Medical Genetics, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Ji-jia
authors.initials: JJ
authors.lastname: Liu
authors.forename: Liang-liang
authors.initials: LL
authors.lastname: Fan
authors.forename: Jin-lan
authors.initials: JL
authors.lastname: Chen
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Tan
authors.forename: Yi-feng
authors.initials: YF
authors.lastname: Yang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C420984:TBX20 protein, human
keywords: Atrial septal defect (ASD); CHD-related gene filter; Congenital heart disease (CHD); TBX20; Whole-exome sequencing