A novel variation of PLAGL1 in Chinese patients with isolated ventricular septal defect

Abstract

Aims: Ventricular septal defect (VSD) is the most common congenital heart disease (CHD). A number of genetic studies have linked the gene of PLAGL1 to the etiology of CHD. The present study aimed to identify potential pathogenic mutations for PLAGL1 and to provide insights into the etiology of isolated VSD.

Methods: Case-control mutational analysis was performed in 300 patients with isolated VSD and 300 healthy controls. Two protein-coding extons of PLAGL1 and their partial flanking intron sequences were amplified by polymerase chain reaction and sequenced on an ABI3730 Automated Sequencer. CLC workbench software was used to compare the conservatism of PLAGL1 protein with other multiple species.

Results: Neither missense nor frame-shift mutations were detected in two protein-coding extons of PLAGL1. But a novel synonymous variation (c.486A>G, p. E162E) was detected in protein-coding exon-2. The glutamic that translated with the mutational codon is conservative when compared with other species.

Conclusions: We detected a synonymous variation in the protein-coding exon-2 of PLAGL1 in isolated VSD patients. It is possible that the etiology of isolated VSD might not be directly linked with this mutation, but might be associated with other patterns of gene expression regulation in PLAGL1, such as in the methylation-dependent manner.

FIG. 1.

A synonymous variation (p. E162E) in the protein isoform 2 of PLAGL1 is identified in this study and is indicated by an arrow (upper). Electropherogram of the identified variation at the position 486 (A>G) of PLAGL1 gene as an A/G double peak is shown by an arrow (lower).

FIG. 2.

Multiple-sequence alignment of partial amino acid sequence of PLAGL1 protein in different species is shown. The alignment data indicate that glutamate at position 162 (indicated by an arrow) is conserved in different species in the PLAGL1 protein.