SNP Shot: Genomic Insights

Spinocerebellar ataxia type 1 (SCA1) is a disease causing a gradual decline in motor skills. The initial symptoms often involve impaired coordination and balance, known as ataxia. Further symptoms can include difficulties with speech and swallowing, muscle stiffness (spasticity), and weakness of the eye muscles (ophthalmoplegia). This eye muscle weakness results in involuntary, rapid eye movements (nystagmus). Furthermore, individuals with SCA1 may experience cognitive impairment, affecting their ability to process, learn, and remember information.

As SCA1 progresses, affected individuals may develop sensory neuropathy, characterized by numbness, tingling, or pain in the limbs. Other potential complications include uncontrolled muscle contractions (dystonia), muscle wasting (atrophy), and muscle twitching (fasciculations). In rare instances, individuals affected for many years may experience rigidity, tremors, and involuntary jerky movements (chorea).

The onset of SCA1 symptoms usually occurs in early adulthood, but the range can vary from childhood to late adulthood. Survival time following the appearance of initial symptoms is typically between 10 and 20 years.

Inheritance:

SCA1 follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is needed to cause the condition. Typically, an affected individual inherits the mutated gene from a parent who also has SCA1. However, some individuals develop SCA1 even without a family history of the disorder. The severity and onset of the disease can vary among those affected due to the increased length of CAG trinucleotide repeats on the altered ATXN1 gene. Each subsequent generation can experience an earlier disease onset which correlates with a larger number of CAG repeats. This is called anticipation and is more commonly seen when a child inherits the mutated gene from their father versus their mother. Individuals with around 35 CAG repeats on the ATXN1 gene do not usually develop SCA1 but may have children with the disease. As the gene is passed down to each generation, the number of repeats can increase to 40 or more, which is then considered SCA1.