A new view on the link between a gene called SORBS2 and congenital heart disease has been published today eLife, with findings that may help explain the cause of the disease in some patients.
Some people with congenital heart disease missing part of the long arm of chromosome 4, also known as chromosome 4q. Chromosomes are filiform structures formed by DNA. When part of the chromosome is missing, it means that some of the people located in this section are also lost. Previous studies have been related heart defects related to 4q chromosome suppression syndrome with a missing copy of the HAND2 gene found on chromosome 4 and important for heart development. But not all heart defect patients lack HAND2, suggesting that other genes will also be involved.
“A previous study of a patient with congenital heart disease suggested that mutations in a gene called SORBS2 could be responsible, but this finding has yet to be confirmed,” explains lead author Fei Liang, a physician in the Care Unit. Neonatal Intensive Care Units at Shanghai Children’s Medical Center, China.
To explore the potential role of SORBS2 in congenital heart disease, Liang and colleagues suppressed the gene in the development of laboratory-cultured human heart cells. This led to the development of heart cells abnormally and interfered with the ability of heart muscle cells to experience the necessary changes in gene expression.
Additional team studies in genetically modified mice showed that lack of SORBS2 resulted in the absence or duplication of the wall between the two upper chambers of the heart in 40% of the embryos. This duplication is a condition known as double atrial septum. However, the effect was much milder compared to human heart defects, suggesting that SORBS2 may be a congenital heart disease gene of “small effect size,” that is, it plays a role. lower in the disease.
The team further examined how the lack of SORBS2 may affect gene expression in both mice and human cells. Their results revealed how levels of other genes and proteins rise or fall in response to the lack of SORBS2, which ultimately causes heart defects and damage.
Finally, they found that rare and harmful variants of the SORBS2 gene were significantly enriched in 300 cases of congenital heart disease in which no severe chromosomal aberrations occurred. This provides additional genetic evidence that SORBS2 variants play a role in the cause of general congenital heart disease.
“Our combined studies help explain the cause of congenital heart disease in patients with 4q chromosome suppression syndrome who still have the HAND2 functional gene,” concludes lead author Zhen Zhang, a professor at the Institute of Congenital Pediatrics. Heart Disease and Shanghai Pediatric Translational Medicine Institute for Children Medical Center. “They provide an effective approach to identifying other genes that play a lesser role in congenitals color disease and other multigenic diseases. Interestingly, we found that SORBS2 deficiency can cause a double atrial septal, a very rare heart abnormality related to a condition called paradoxical thromboembolism. The exact causes of this anomaly are currently unknown and we hope that our study will pave the way for further study. ”
Fei Liang et al, SORBS2 is a genetic factor that contributes to heart malformation in patients with 4q deletion syndrome, eLife (2021). DOI: 10.7554 / eLife.67481
Citation: Researchers identify a gene related to congenital heart disease (2021, June 8) retrieved June 8, 2021 from https://medicalxpress.com/news/2021-06-gene-linked-congenital-heart-disease. html
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