title: GATA4 mutations in 357 unrelated patients with congenital heart malformation.
abstract: Congenital heart disease (CHD) represents one of the most common birth defects, but the genetic causes remain largely unknown. Mutations in GATA4, encoding a zinc finger transcription factor with a pivotal role in heart development, have been associated with CHD in several familial cases and a small subset of sporadic patients. To estimate the pathogenetic role of GATA4 in CHD, we screened for mutations in 357 unrelated patients with different congenital heart malformations. In addition to nine synonymous changes, we identified two known (A411V and D425N) and two novel putative mutations (G69D and P163R) in five patients with atrial or ventricular septal defects that were not seen in control subjects. The four mutations did not show altered GATA4 transcriptional activity in synergy with the transcription factors NKX2-5 and TBX20. Our data expand the spectrum of mutations associated with cardiac septal defects but do not support GATA4 mutations as a common cause of CHD.
authors.affiliation: Heart Centre for Children, The Children's Hospital at Westmead, Westmead, Australia.
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Butler
authors.forename: Giorgia
authors.initials: G
authors.lastname: Esposito
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Blue
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cole
authors.forename: Mauro W
authors.initials: MW
authors.lastname: Costa
authors.forename: Leigh B
authors.initials: LB
authors.lastname: Waddell
authors.forename: Gina
authors.initials: G
authors.lastname: Walizada
authors.forename: Gary F
authors.initials: GF
authors.lastname: Sholler
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Kirk
authors.forename: Michael
authors.initials: M
authors.lastname: Feneley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: David S
authors.initials: DS
authors.lastname: Winlaw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009154:Mutation; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D055815:Young Adult; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D020825:T-Box Domain Proteins; C420984:TBX20 protein, human; D014157:Transcription Factors