Novel GATA4 mutations in patients with congenital ventricular septal defects
| Autor: | Wei Zhang, Wei-Yi Fang, Xu Liu, Xiao-Zhong Chen, Yi-Qing Yang, Xing-Yuan Liu, Xiao-Zhou Wang, Juan Wang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Heart Septal Defects
Ventricular Male congenital hereditary and neonatal diseases and abnormalities Heart disease DNA Mutational Analysis Molecular Sequence Data Biology medicine.disease_cause Bioinformatics Pathogenesis Clinical Research medicine Humans Missense mutation genetics Amino Acid Sequence transcription factor Genetics Mutation Heart septal defect Base Sequence GATA4 Genetic heterogeneity Exons General Medicine medicine.disease Introns GATA4 Transcription Factor Pedigree ventricular septal defect Phenotype Child Preschool Etiology Female Sequence Alignment |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1234-1010 |
| DOI: | 10.12659/msm.882877 |
| Popis: | Summary Background Ventricular septal defect (VSD) is the most prevalent type of congenital heart disease and is a major cause of substantial morbidity and mortality in infants. Accumulating evidence implicates genetic defects, especially in cardiac transcription factors, in the pathogenesis of VSD. However, VSD is genetically heterogeneous and the genetic determinants for VSD in most patients remain to be identified. Material/Methods A cohort of 230 unrelated patients with congenital VSD was included in the investigation. A total of 200 unrelated ethnically matched healthy individuals were recruited as controls. The entire coding region of GATA4, a gene encoding a zinc-finger transcription factor essential for normal cardiac morphogenesis, was sequenced initially in 230 unrelated VSD patients. The available relatives of the mutation carriers and 200 control subjects were subsequently genotyped for the presence of identified mutations. Results Four heterozygous missense GATA4 mutations of p.Q55R, p.G96R, p.N197S, and p.K404R were identified in 4 unrelated patients with VSD. These mutations were not detected in 200 control individuals nor described in the human SNP database. Genetic analysis of the relatives of the mutation carriers showed that in each family the mutation co-segregated with VSD. Conclusions These findings expand the mutation spectrum of GATA4 linked to VSD and provide new insight into the molecular etiology responsible for VSD, suggesting potential implications for the genetic diagnosis and gene-specific therapy for VSD. |
| Databáze: | OpenAIRE |
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