Résumé
Objective · To explore the correlation between variants located in 3' untranslated regions (3'UTR) of NOTCH1 and JAG1 genes and conotruncal heart defects (CTD). Methods · Six hundred CTD children without 22q11 deletion and three hundred healthy children were enrolled in this hospital-based case-control study. Variants located in the 3'UTR regions of NOTCH1 and JAG1 genes were detected by high-throughput sequencing. The accuracy of the variants were verified by PCR and Sanger sequencing. Online software PicTar, TargetScan and microRNA.org were used to make functional predictions. Results · One mutation and three SNPs were found in the 3'UTR of NOTCH1. Three mutations and six SNPs were found in the 3'UTR of JAG1. The genotypic distributions of two SNPs (rs3840074 and rs8708) located in JAG13'UTR between CTD group and the controls were statistically significant (both P<0.05). Results of prediction showed that all the four mutations and two meaningful SNPs could bind to microRNA. Conclusion · The variants located in 3'UTR regions of NOTCH1 and JAG1 genes may be related to the occurrence of CTD.
Résumé
Objective To explore the correlation between mutations in the promoter region of TBX1 gene and conotruncal heart defects. Methods A total of 621 children with conotruncal heart defects were recruited. Multiplex ligation-dependent probe ampliifcation (MLPA) was used to detect the copy numbers of chromosomal region 22 q 11 . 2 . Children with 22 q 11 . 2 deletion were excluded. Polymerase chain reaction ampliifcation (PCR) and gene sequencing were applied to analyze promoter region of TBX 1 (-2000 ..+1 ) in 605 children with conotruncal heart defects without 22 q 11 . 2 deletion and 588 healthy children. Bioinformatics software was used to predict and analyze the function of the variable loci. Results There were mutations in the promoter region of TBX 1 gene in children with conotruncal heart defects, including 3 single nucleotide polymorphisms (SNP) sites and 7 rare loci. The incidence of mutation was 1 . 7%. The analysis of 7 rare loci by AliBaba 2 . 1 to showed that 3 of them may inlfuence the combination of trans-acting factors and cis-acting elements of the promoter of TBX 1 gene. Conclusion The mutation in the TBX 1 promoter region may be related to the occurrence of conotruncal heart defects.