In a groundbreaking study, researchers from Niigata University and the National Center of Neurology and Psychiatry (NCNP) have identified critical thresholds for CAG repeat units (RU) in the CACNA1A gene linked to Spinocerebellar Ataxia Type 6 (SCA6). By analyzing data from 2,768 patients, the team uncovered significant correlations between the number of repeat units, age of onset, and family history. The findings offer new insights into diagnosing and counseling patients with SCA6, emphasizing the importance of precise genetic evaluation.

Key Findings on CAG Repeat Units and SCA6

In an extensive investigation conducted during the autumn of 2025, scientists explored the relationship between CAG repeat units in the CACNA1A gene and the occurrence of SCA6. They discovered that individuals with 18 or fewer repeat units exhibited a lower incidence of familial cases. However, as the number of repeats increased to 19 or more, the likelihood of a family history also rose, stabilizing at 23 or more repeats. Researchers then developed a predictive model for the correlation between repeat units and the age of onset for definitive SCA6 cases with 23 or more repeats. Their analysis revealed that over 90% of individuals with 21 or more repeats fell within the predicted age range. In contrast, those with 19-20 repeats showed a decreasing proportion within this range, while most cases with 18 or fewer repeats lay outside it.

Furthermore, the study employed multiple regression analysis to assess the influence of opposite alleles on the age of onset. For cases with expanded alleles of 21 and 22 repeats, the opposite alleles played a role in determining the age of onset. However, for individuals with 23 or more expanded alleles, no such association was found. Notably, cases with 19-20 expanded alleles had a significantly higher proportion of opposite alleles with 19 or more repeats compared to those with 23 or more expanded alleles.

Dr. Hatano and Dr. Ishihara emphasized the practical implications of these findings. "When evaluating ataxia patients with 21 or more repeats, it is reasonable to consider SCA6," they explained. "However, for patients with 19-20 repeats, careful consideration is necessary to determine if it is SCA6, especially when the opposite allele is also in this range."

Implications for Diagnosis and Genetic Counseling

This research provides invaluable guidance for clinicians and genetic counselors. It highlights the necessity of a nuanced approach to diagnosing SCA6, particularly for borderline cases with 19-20 repeat units. The study underscores the importance of considering both the number of repeat units and the presence of specific opposite alleles in making accurate diagnoses. As a result, healthcare professionals can offer more informed and personalized advice to patients and their families, improving outcomes and quality of life.