Written by Dr. Marija Cvetanovic Edited by Dr. Larissa Nitschke
Expanded CAG repeats are the cause of Huntington’s disease (HD) and several spinocerebellar ataxias (SCAs). Longer inherited CAG expansions correlate with the earlier disease onset and worse symptoms. We know from past research that these expansions are unstable and become longer from one generation to the next.
This study by Mouro Pinto and colleagues shows that repeat expansions also keep getting longer throughout life in patients affected with HD and SCA1 in many cells, including brain, muscle, and liver cells.
Expansion of CAG repeats in different human genes cause several neurodegenerative diseases. This includes Huntington’s disease (HD) and several spinocerebellar ataxias (SCAs). These long CAG repeats in disease genes tend to be unstable in the sperm and egg cells. This instability in sperm and egg cells can result in either longer repeat tracts (expansions) or shorter ones (contractions) in the children of affected patients. Unfortunately, CAG repeats more often expand than shrink. This results in a worse disease in the affected children, with earlier onset and more severe symptoms than their parents.
However, repeat instability and expansion of repeats are not confined to the sperm and egg cells. It can occur in many cells in a patient’s body. This ongoing expansion that occurs in other body cells is called somatic expansion.
As affected patients age, the ongoing somatic expansion, especially in the brain, may accelerate the onset of neuronal dysfunction and loss of neurons and. This may worsen the disease progression. This has been previously shown in mouse models and patients with HD. However, those studies examined expansion in only a few brain regions and tissues outside the brain (called peripheral tissues).
In this study lead by Dr. Vanessa C. Wheeler, the authors systematically examined repeat instability in 26 different regions of the brain, post-mortem cerebrospinal fluid (CSF) and nine peripheral tissues, including testis and ovaries from seven patients with HD and one patient with SCA1.Continue reading “Elongating expansions in HD and SCA1”