GATA4 sequence variants in patients with congenital heart disease. J Med Genet 2007 Dec;44(12):779-83
Date
12/07/2007Pubmed ID
18055909Pubmed Central ID
PMC2652815DOI
10.1136/jmg.2007.052183Scopus ID
2-s2.0-37249090635 (requires institutional sign-in at Scopus site) 189 CitationsAbstract
BACKGROUND: Recent reports have identified mutations in the transcription factor GATA4 in familial cases of cardiac septal defects. The prevalence of GATA4 mutations in the population of patients with septal defects is unknown. Given that patients with septal and conotruncal defect can share a common genetic basis, it is unclear whether patients with additional types of CHD might also have GATA4 mutations.
AIMS: To explore these questions by investigating a large population of 628 patients with either septal or conotruncal defects for GATA4 sequence variants.
METHODS: The GATA4 coding region and exon-intron boundaries were investigated for sequence variants using denaturing high-performance liquid chromatography or conformation-sensitive gel electrophoresis. Samples showing peak or band shifts were reamplified from genomic DNA and sequenced.
RESULTS: Four missense sequence variants (Gly93Ala, Gln316Glu, Ala411Val, Asp425Asn) were identified in five patients (two with atrial septal defect, two with ventricular septal defect and one with tetralogy of Fallot), which were not seen in a control population. All four affected amino acid residues are conserved across species, and two of the sequence variants lead to changes in polarity. Ten synonymous sequence variants were also identified in 18 patients, which were not seen in the control population.
CONCLUSIONS: These data suggest that non-synonymous GATA4 sequence variants are found in a small percentage of patients with septal defects and are very uncommonly found in patients with conotruncal defects.
Author List
Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz EAuthor
Aoy Tomita Mitchell PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid MotifsAmino Acid Substitution
Cohort Studies
Conserved Sequence
GATA4 Transcription Factor
Genetic Heterogeneity
Heart Defects, Congenital
Heart Septal Defects
Humans
Mutation, Missense
Penetrance
Point Mutation
Prospective Studies
Protein Structure, Tertiary
Tetralogy of Fallot
