Clinical Features And Genetic Analysis Of Pathogenic Dynamic Mutation Of Patients With Spinocerebellar Ataxia

Aims: To analyse clinical and genetic features of spinocerebellar ataxia(SCA)patients.To investigate phenotype-genotype relationship of SCA patients.To establish the diagnostic approach in genetic testing for SCA patients.Methods: Detailed history inquiry and professional neurologic examination were performed to SCA patients.International Cooperative Ataxia Rating Scale(ICARS)was conducted to assess the disease condition.Polymerase Chain Reaction(PCR)and fragment analysis were carried out to detect pathogenic dynamic mutations in SCA patients and pre-clinical patients.Results: 477 SCA patients and their family members were enrolled in this study.There were 262 autosomal dominant SCA pedigrees and 92 sporadic patients.Among 262 autosomal dominant SCA pedigrees,27(10.31%)were positive for SCA1,26(9.92%)were positive for SCA2,181(69.08%)were positive for SCA3,7(2.67%)were positive for SCA6,1(0.38%)was positive for SCA12,1(0.38%)was positive for DRPLA,19(7.25%)were genetically unidentified.Among 92 sporadic SCA patients,4(4.35%)were positive for SCA1,1(1.09%)was positive for SCA2,6(6.52%)were positive for SCA3,1(1.09%)was positive for SCA6,1(1.09%)was positive for SCA8,2(2.17%)were positive for SCA12,77(83.70%)were genetically unidentified.Expanded nucleotide repeats of SCA7,SCA10,SCA17,SCA31 and SCA36 were not discovered.Conclusions: 1.SCA3 has the highest prevalence in Chinese Han SCA patients in mainland China,followed by SCA1,SCA2 and SCA6.2.Hyporeflexia/areflexia and tremor are positive predictors for SCA2,and nystagmus is negative predictor for SCA2.SCA6 has a relatively later onset age than SCA1,SCA2 and SCA3.Some SCA6 patients in our study can present extracerebellar features.3.We expanded the range of pathogenic CAG trinucleotide repeat of SCA12.4.Negative correlations were identified between expanded CAG repeat length of SCA1,SCA2,SCA3 and age at onset(P<0.05)in this study.5.A screening strategy was established based on clinical manifestations and the frequencies of SCA genes.Screening for SCA3 should be conducted first.SCA1 and SCA2 come second.Then SCA6 should be screened.Next is SCA8,SCA12 and DRPLA.SCA7,SCA17,SCA10,SCA31,SCA36 and other SCA subtypes due to conventional mutation should be screened finally.Patients with distinguishing phenotypes should give priority to screening specific SCA subtypes with dynamic mutation.