People who have duplications in a region of chromosome 16 (16p13.1) that is present in approximately 1 in 1000 individuals have a 12-fold increased risk of thoracic aortic aneurysms leading to a tear in the aorta, or acute aortic dissections. An estimated 10000 people die annually from thoracic aortic aneurysms and dissections (TAAD) in the United States, where TAAD have ranked as high as the 15th leading cause of death. The study, led by genetic researchers at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine, was published on 16 June 2011 in the open-access journal PLoS Genetics.
There are regions of the human DNA that are deleted or duplicated, referred to as copy number variants (CNVs). These CNVs can manifest as a loss of the number of copies of a gene from two to one or as additional copies of a gene from two to three.
“We are just starting to understand copy number variants and their link to disease,” said Dianna Milewicz, senior author and professor at UTHealth. “This is the first recurrent CNV discovered to be associated with thoracic aortic aneurysms and dissections. In addition, it is the first recurrent copy number variant to cause a predisposition to more than one disorder, neuropsychiatic conditions and thoracic aortic disease.”
Duplications of the 16p13.1 region have been associated with a variety of neuropsychiatric disorders, such as schizophrenia and attention-deficit hyperactivity disorder (ADHD). One of the genes in this region is MYH11, which is known to affect the smooth muscle cell tissue in major arteries in the body, including the thoracic aorta. A weakness in the lining of the thoracic aorta, which carries blood from the heart to the rest of the body, can lead to an aneurysm and/or dissection, which can cause sudden death.
“The results of this study could affect clinical care because it appears patients with 16p13.1 duplications have an aggressive form of the thoracic aortic disease that causes aneurysms to dissect at smaller diameters,” Milewicz said. “Also, once doctors are able to use the entire genome, people with duplications in 16p13.1 would need to have their aortas monitored.”
The team led by Milewicz includes researchers from UTHealth, Baylor College of Medicine, the Texas Heart Institute and GenTAC investigators from Johns Hopkins University, Weill Medical College of Cornell University and the National Heart, Lung and Blood Institute.