The Analysis Of FMR1 Gene Permutation In Sporadic Spinocerebellar Ataxia And Multiple System Atrophy Patients

Background Fragile X-associated tremor-ataxia syndrome (FXTAS) is a neurodegenerative disease characterized by progressive cerebellar ataxia and intention tremor. FXTAS is principally characterized with progressive intention tremor and gait ataxia, with more variable associated features of cognitive decline, parkinsonism, dysautonomia, peripheral neuropathy and psychosis. The pathogenic basis of FXTAS is the formation of intranuclear inclusions in neurons and astrocytes. FMR1 gene located in Xq27.3, has a polymorphic region containing CGG repeats in a non-coding part of the first exon. Individuals with alleles between 55 and 200 CGG repeats are called premutated carriers. FMR1PM can lead to FMR1mRNA activity levels increase and intranuclear inclusions form, some patients develop FXTAS.Currently, there is not specific epidemiological study of FXTAS. FMR1PM alleles are frequent in the general population, with prevalence of 1:259 female and 1:813 male. It is more prevalent in Mediterranean groups, while it is less common in Asian populations. Many studies suggest that the frequency of premutation alleles was 13 times greater in man with late-onset cerebellar ataxia than expected on the basis of its prevalence in the general population. Five carriers of premutation alleles were identified among 663 patients with a prior diagnosis of MSA-C. Currently, there is not Large-scale research of FMR1PM in Asian cerebellar ataxia patients. In Singapore, Tan etal.did not found FMR1PM in their study.Till now, there are no relevant reports in mainland China.Objective Undertaken the premutation analysis of FMR1 in patients of Chinese who presented with spinocerebellar ataxia and multiple system atrophy.Method we analyzed FMR1PM for 68 SCA,32 MSA and 100 normal control by PCR,8% denaturing polyacrylamide gel and capillary electrophoresis methods. Then we undertaken Southern blot for FMR1 gene which is homozygous form 23 cases by capillary electrophoresis.Result we did not found FMR1PM (CGG>55) in mutation analysis of FMR1PM for 68 SCA,32 MSA and 100 normal control by PCR,8% denaturing polyacrylamide gel and capillary electrophoresis and Southern blot. In SCA and MSA patients, the CGG repeats ranged from 15 to 44, of which the most common CGG repeat unit was 28 and in normal controls the CGG repeats ranged from 21-40, most common CGG repeat unit was 27.Conclusions1 First established the mutation detection for the duplication mutation of FMR1CGG by PCR-capillary electrophoresis-southern blot technique in china.2 The FMR1PM in Chinese sporadic spinocerebellar ataxia patients may be rare.3 The FMR1PM in Chinese multiple system atrophy patients may be rare.