NEW YORK (GenomeWeb) – Researchers from China and Canada have uncovered a handful of rare copy number variants involved in a congenital heart condition called conotruncal heart disease in Chinese individuals.
Using an array-based approach, the team profiled copy number patterns in more than 100 Chinese people with conotruncal heart disease, a group of conditions marked by congenital heart defects that affect the way blood flows out of the heart. The analysis focused on individuals who did not have a recurrent chromosome 22 deletion syndrome, which has been implicated in a type of conotruncal heart disease called tetralogy of Fallot.
As it reported in Npj Genomic Medicine today, the team detected rare de novo CNVs in more than 9 percent of the Chinese individuals with conotruncal heart disease. In three of the 10 individuals with heart disease-associated CNVs, the heart symptoms appeared to be part of a broader syndrome suspected of influencing cardiac development.
"All three of these patients carried a de novo CNV harboring genes potentially linked to cardiac development that would be considered pathogenic," senior author Brian Chung, a pediatrics and adolescent medicine researcher at the University of Hong Kong, and his co-authors wrote. "The other seven large genic CNVs, all very rare and in patients with few or no reported extracardiac features, would represent variants of unknown clinical significance."
For their analysis, the researchers started with 137 Chinese adults who'd visited a congenital heart disease clinic. After excluding individuals with the recurrent chromosome 22 deletion, they were left with 116 participants (95 individuals with tetralogy of Fallot and 21 with a condition called pulmonary atresia with VSD), who were genotyped for CNVs on Affymetrix arrays.
High confidence CNV calls were available for 108 individuals. By comparing CNV patterns in these individuals with those in nearly 4,000 Caucasian and almost 2,000 Singapore Chinese controls, the team homed in on 10 large CNVs that appeared to be rare and de novo in the Chinese patients.
Of those, the researchers focused on three large de novo CNVs suspected of being syndromic: a duplication involving a region of chromosome 2 that contains the ZEB2 gene, a chromosome 17 deletion affecting the NXN gene, and chromosome 13 deletion spanning dozens of genes, including several candidate cardiac development contributors.
The study's authors noted that "[l]arger samples of Chinese origin will be required to determine whether the genome-wide [rare CNV] distribution differs from that found in predominantly European [congenital heart disease] cohorts."