SNP Shot: Genomic Insights

Dentatorubral-pallidoluysian atrophy (DRPLA) is a brain disease that worsens over time. It leads to uncontrolled movements, changes in mood and behavior, and difficulties with thinking and memory. While the typical age of onset is around 30, DRPLA can manifest at any point between infancy and middle age.

The symptoms of DRPLA can vary depending on whether it starts in childhood or adulthood. In children (before age 20), common symptoms include myoclonus (sudden, involuntary muscle jerks), seizures, behavioral issues, intellectual disability, and ataxia (problems with balance and coordination). In adults (after age 20), the most common signs are ataxia, choreoathetosis (uncontrollable writhing movements of the limbs), psychiatric problems such as delusions, and dementia (decline in cognitive function).

Inheritance:

DRPLA follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the disease. Most people with DRPLA have one affected parent. The ATN1 gene, responsible for DRPLA, contains a repeating CAG sequence. As the gene is passed down through generations, the number of CAG repeats often increases. Larger expansions of these repeats are generally linked to an earlier onset and more severe symptoms, a phenomenon known as anticipation. Anticipation is typically more pronounced when the mutated ATN1 gene is inherited from the father (paternal inheritance) compared to inheritance from the mother (maternal inheritance).