Scientists discover gene linked to abnormal organ placement and congenital heart defects microbiologystudy

New research by KAUST scientists has identified that the gene “CIROZ” is responsible for pediatric heart defects and the misplacement of internal organs. The findings come from working with multiple institutes worldwide, including two universities and two hospitals in the Kingdom. It provides new information on heritable diseases, which have a higher rate in Saudi Arabia than worldwide.

Joining a team of scientists and medical doctors from leading research hospitals and medical institutions across the region including Saudi Arabia, KAUST Professor Bruno Reversade explains the implications of the unique Middle Eastern demography in a new perspective written in Nature Genetics. The perspective refers to the identification of several genes related to inherited diseases that emerged from studying populations in the greater Middle East.

In a complementary research paper, writing with the same scientists from Saudi Arabia, he led an international team of scientists from 13 countries who report in The American Journal of Human Genetics that mutations in the gene CIROZ cause severe heart defects at birth. The gene was known to scientists before but as C1orf127, and its function in the human body was never understood. The new name is an abbreviation that reflects its function.

“Many diseases go without a diagnosis, and for most of the conditions, the available treatments are to manage the symptoms. By identifying a single gene responsible, we can now focus our research efforts on preventive strategies to reduce the disease burden and to find curative therapies,” said Naif Almontashiri, an associate professor at Taibah University who also authored the two studies and is conducting a research study on the genetic landscape of congenital heart diseases in Saudi Arabia.

By examining samples from 16 patients from 10 families, including four families from Saudi Arabia, the scientists found that CIROZ has an essential role in symmetry breaking in embryonic development and how its inactivation brings about congenital heart defects.

From the outside, our bodies look symmetrical. On the left and right are eyes and ears equally distant from the nose, while arms and legs grow from both sides. Inside, however, our bodies show a fair amount of asymmetry—the heart is on the left, while the liver is on the right. Even at the stage when our bodies are no bigger than a raspberry, cells start to shift inside the embryo so that all organs and tissues begin growing in their proper place.

The loss of proper asymmetry is known as “heterotaxy,” a condition that is believed to occur in 1 of every 10,000 births worldwide. For many, heterotaxy is asymptomatic and causes no change in the quality of life. For others, however, the health problems are life-threatening, as five of the 16 individuals examined in the study never celebrated their first birthday due to heart defects.

Looking at the same gene in different animals, the study finds CIROZ is especially pertinent in the proper development of mammals including humans, suggesting its function has changed during evolution. This finding shows the limitation of using animals to study human embryogenesis and the importance of scientists having access to patient samples.

“Inherited diseases are most prevalent in the Middle East, and many remain unexplained. Our goal is to assist in the development of better diagnostic tools for orphan genetic conditions in the Kingdom. To do this, we constantly work with Saudi hospitals to build a strong network of research partnerships that benefits patients and their families,” said Reversade.