title: Somatic mutations in NKX2–5, GATA4, and HAND1 are not a common cause of tetralogy of Fallot or hypoplastic left heart.
abstract: The majority of congenital heart disease (CHD) occurs as a sporadic finding, with a minority of cases associated with a known genetic abnormality. Combinations of genetic and environmental factors are implicated, with the recent and intriguing hypothesis that an apparently high rate of somatic mutations might explain some sporadic CHD. We used samples of right ventricular myocardium from patients undergoing surgical repair of tetralogy of Fallot (TOF) and hypoplastic left heart (HLH) to examine the incidence of somatic mutation in cardiac tissue. TOF is a common form of cyanotic CHD, occurring in 3.3 per 10,000 live births. HLH is a rare defect in which the left side of the heart is severely under-developed. Both are severe malformations whose genetic etiology is largely unknown. We carried out direct sequence analysis of the NKX2–5 and GATA4 genes from fresh frozen cardiac tissues and matched blood samples of nine TOF patients. Analysis of NKX2–5, GATA4, and HAND1 was performed from cardiac tissue of 24 HLH patients and three matched blood samples. No somatic or germline mutations were identified in the TOF or HLH patients. Although limited by sample size, our study suggests that somatic mutations in NKX2–5 and GATA4 are not a common cause of isolated TOF or HLH.
authors: Kids Heart Research, The Children’s Hospital at Westmead, Sydney, Australia.
authors: Giorgia
authors: G
authors: Esposito
authors: Tanya L
authors: TL
authors: Butler
authors: Gillian M
authors: GM
authors: Blue
authors: Andrew D
authors: AD
authors: Cole
authors: Gary F
authors: GF
authors: Sholler
authors: Edwin P
authors: EP
authors: Kirk
authors: Paul
authors: P
authors: Grossfeld
authors: Benjamin M
authors: BM
authors: Perryman
authors: Richard P
authors: RP
authors: Harvey
authors: David S
authors: DS
authors: Winlaw
mesh_terms: D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013771:Tetralogy of Fallot / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D014157:Transcription Factors; C484170:GATA4 protein, human; C095552:NKX2-5 protein, human; C097341:helix-loop-helix protein, eHAND