title: Novel NKX2-5 mutations in patients with familial atrial septal defects.
abstract: Atrial septal defect (ASD) is a common cardiovascular malformation and an important contributor to substantial morbidity and mortality. Increasing evidence demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor crucial to cardiogenesis, is a significant genetic determinant for congenital ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients remains largely unknown. In the current study, the entire coding region of NKX2-5 was sequenced initially for 58 unrelated probands with familial ASD. The relatives of the probands harboring identified mutations and 200 unrelated control individuals were subsequently genotyped. Three novel heterozygous NKX2-5 mutations (p.P43GfsX59, p.C46 W, and p.S179F) were identified respectively in three families with autosomal dominantly inherited ASD. These mutations, absent in 200 control individuals, cosegregated with ASD in the families that had complete penetrance. The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xing-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Zhang
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Wang
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Zheng
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006344:Heart Septal Defects, Atrial / Q000000981:diagnostic imaging / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D014463:Ultrasonography
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors