title: [Genetic screening for novel GATA4 mutations associated with congenital atrial septal defect].
abstract: OBJECTIVE
  To screen the gene GATA4 for novel mutations associated with congenital atrial septal defect (ASD).
  
  
  METHODS
  The clinical data and peripheral venous blood specimen from 85 unrelated subjects with congenital ASD were collected and analyzed in contrast to 200 healthy individuals. The coding exons and the exon/intron boundaries of GATA4 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination procedure. The obtained sequences were aligned with those publicized in GenBank with the help of programme BLAST to identify the sequence variations. The software Clustal W was applied to analysis of the conservation of altered amino acids.
  
  
  RESULTS
  Three novel heterozygous missense GATA4 mutations were identified in 3 of 85 ASD patients, respectively. Namely, the triplet substitutions of ATG for GTG at codon 267, GCC for ACC at codon 354, and CAA for CCA at codon 407, predicting the conversions of valine into methionine at amino acid residue 267 (V267M), threonine into alanine at amino acid residue 354 (T354A), and proline into glutamine at amino acid residue 407 (P407Q), were identified. No mutation was detected in 200 healthy controls. A cross-species alignment of GATA4 encoded protein sequences showed that the valine at amino acid residue 267 and proline at amino acid residue 407 were completely conserved evolutionarily.
  
  
  CONCLUSIONS
  Three novel heterozygous missense GATA4 mutations were identified in patients with congenital ASD, which reveals new molecular etiology responsible for ASD, and contributes to the early prophylaxis and therapy for ASD.
authors.affiliation: Department of Cardiology, Tongji University Affiliated East Hospital, Shanghai 200120, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Xin-ming
authors.initials: XM
authors.lastname: Li
authors.forename: Yuan-feng
authors.initials: YF
authors.lastname: Xin
authors.forename: Li-jie
authors.initials: LJ
authors.lastname: Wang
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Xu
authors.forename: Da-yi
authors.initials: DY
authors.lastname: Hu
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D050991:GATA4 Transcription Factor / Q000235:genetics*; D005820:Genetic Testing; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense
chemical_list: D050991:GATA4 Transcription Factor