Abstract:

Objective To screen mutations in 3′UTR region of TBX1C gene of patients with conotruncal heart defects (CTHD) and explore the possible mechanism that how mutations in this region affect the expression and function of TBX1C gene. Methods Fifty-two CTHD patients without 22q11.2 microdeletion (the CTHD group) and eighty nine healthy children (the control group) were selected. Sequences of 3′UTR region of TBX1C gene were amplified by the PCR and all PCR products were sequenced by both forward and reverse sequencing. Sequencing results were compared to TBX1C 3′UTR sequences in GenBank (NM 080647.1) and possible mutations were screened. Online software PicTar and TargetScan were used to predict microRNA (miRNA) which could bind to 3′UTR region of TBX1C gene. The effect of mutations in 3′UTR region of TBX1C gene on the expression of miRNA-regulated TBX1C gene was analyzed. Results A mutation of c.*164_*165insC was found in patients of the CTHD group. A cytosine was inserted between the 164th and 165th nucleotide from the termination codon. This mutation is a new mutation since it did not exist in patients of the control group and was not reported by other studies. Results of prediction showed that there were ten miRNAs which could bind to 3′UTR region of TBX1C gene and this mutation did not locate in binding regions of ten miRNAs and 3′UTR region of TBX1C gene. Conclusion A new mutation, c.*164_*165insC, exists in 3′UTR region of TBX1C gene. This mutation may affect the spatial configuration of binding of 3′UTR region of TBX1C gene and miRNAs and further affect the regulatory effect of miRNAs on the expression of TBX1C gene.

Key words: conotruncal heart defect, TBX1 gene, gene mutation, 3′UTR, microRNA