Genetic and clinical profiles in a large cohort of Chinese individuals with spinocerebellar ataxia type 1

Abstract Background Spinocerebellar ataxia type 1 (SCA1) is the third most common type of spinocerebellar ataxia in China. However, data about Chinese SCA1 patients are limited. This study aims to provide a detailed description of the phenotype and genotype of Chinese SCA1 individuals and guide the clinical practice. Methods A total of 110 SCA1 individuals from 79 pedigrees and 123 unrelated normal controls were recruited. Sanger sequencing, SfaNI restriction and TA cloning were used for the determination of the CAG repeat size and the intrinsic structure. Clinical data including scale scores, magnetic resonance imaging and electromyography were collected. Results Interrupted pathogenic alleles occurred in 5.5% of the SCA1 individuals and caused later disease onset (p < 0.0001). The average age at onset (AAO) was 38.1 ± 10.1 years, inversely correlated with the expanded CAG repeats (expCAGs), best fitted with exponential models. The mean ± SD of the longest uninterrupted expCAG repeat number was 48.3 ± 4.6 and could explain 65.4% of the AAO variance, making an increasement of 28.0% compared to the total CAG repeats. Longer disease duration and larger expCAG size were associated with higher scale scores and smaller brainstem relative volumes. Conclusions This study described the genetic and clinical profiles of Chinese SCA1 individuals, revealed the impact of interruptions in expCAGs to AAO and made an inter-population comparison.