Clinical Characteristics Of Spinocerebellar Ataxia 2(SCA2) And Multiple System Atrophy (MSA) And Analysis Of ATXN2 Gene Mutation

Objective:To identify the genetic,clinical and imaging characteristics of SCA2 and MSA in Yunnan Province.Through carrying out ATXN2 gene screening for patients and family members,we can find the features of CAG trinucleotide repeats and repeative sequence and explore the correlation with MSA.Besides,we can also diagnose presymptomatic patients,provide basis for differential diagnosis between SCA2 and MSA.Methods:Based on Harding and Gilman diagnostic criteria,thirteen subjects diagnosed as SCA2 and eleven subjects diagnosed as MSA during 2013.1-2016.12 in the hospital were studied retrospectively about their clinical characteristics.We explored the features of CAG trinucleotide repeats of ATXN2 gene and used SPSS Statistics 22.0 to make a statistical analysis.Results:1.Mean age of onset of thirteen SCA2 patients was 39.69±4.97(range from 35 to 50).Mean age of onset of eleven MSA patients was 50.73±6.86(range from 34 to 64).There was significant statistical difference between them.2.Of all the patients,the most common onset symptoms included gait ataxia and dysarthria.Dizziness was also the main onset manifestation of MSA.And involuntary movement was the special onset characteristic of SCA2.After examination,there was no significant difference between the two groups.3.The most common clinical presentations included gait ataxia,dysarthria,bradykinesia,tremor,dizziness,urogenital dysfunction,cognitive and affective disorder.The presentations were different in two disorders:vegetative nerve functional disturbance like dizziness and sexual dysfunction were more common in MSA,however,ophthalmoplegia,fasciculation and slow saccades were only found in SCA2.After inspection,there were significant differences between SCA2 and MSA patients with autonomic dysfunction like dizziness and sexual dysfunction,but other symptoms such as tremor,myotonia,cognitive and affective disorder had no significant difference.4.The most common MRI abnormalities were cerebellar/pontine atrophy and ventrical expansions.Besides,cerebral atrophy,abnormal midbrain signal and white matter ischemia were also found in MSA.5.We carried out ATXV2 gene screening for SCA2 families and MSA patients,the results showed there were three kinds of abnormal CAG trinucleotide repeats among 8 SCA2 family members,namely,35,38 and 40 repeats.However,only 4 patients among them,other people were presymptomatic patients,and people with 35 CAG repeats were normal up to now.Besides,the mode of CAA or other interruptions were undiscovered.The CAG trinucleotide repeats of MSA patients were normal.The repetitive sequences of ATXN2 gene we had found yet included(CAG)8CAA(CAG)4CAA(CAG)8 and(CAG)13 CAA(CAG)8.Conclusions:1.SCA2 and MSA patients had similar clinical manifestations and cranial MRI features,but the age of onset of SCA2 patients was younger and the genetic factors were more common.However,the age of onset of MSA patients was older and the family history was rarely found,in addition,vegetative nerve functional disturbance were more common in MSA patients.2.The abnormal CAG trinucleotide repeats of ATXN2 gene discovered in Yunnan province included 35,38 and 40,in addition,35 repeats had incomplete penetrance,the mode of CAA or other interruptions were undiscovered.The most common CAG trinucleotide repeats were 22 and had CAA interruptions.The CAG trinucleotide repeats and repeatitive sequence of MS A patients were normal.3.Gene detection is the gold standard for the diagnosis of SCA2 patients and also the screesning method for presymptomatic patients.