Studies On The Genetic Mutation, Microstructure Damage Imaging Characteristics On White Matter Brain, Serum α-Synuclein Expression Level Of Spinocerebellar Ataxia Type12

Objective:1) To investigate the CAG trinucleotide repeate expansion and clinicalcharacteristics of the SCA12from the Uygur nationality in Xinjiang Uygur AutonomousRegion;2) This paper determine changes in different positions in one Uyghur SCA12pedigree by measuring the apparent diffusion coefficient (ADC) and fractional anisotropy(FA);3) Discuss Of xinjiang uygur with symptoms of Parkinson’s genetic type spinalcord cerebellar ataxia type12whether the onset of Parkinson’s disease has the same basis,Whether is also caused by abnormal nucleoprotein gather alpha-synapses. Methods:1)According to the Harding standardization, we collected a parentage from the Uygurnationality,13patients were suspectly diagnosed,54“healthy”members were examinedin detail of the Nervous System.They were analyzed by Molecular Genetics and detectedby Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technologyby T-Vector cloning and restriction enzyme cutting, direct Sequencing. the diagnosis ofSCA12was confirmed, Similarly we analyzed the gene mutation about CAGtrinucleotide repeate expansion. and sequencing was used to detect SCA12gene in60theUygur nationality controls;2) DTI was performed on a1.5T scanner, with b=1000s/mm2and15directions. ADC and FA were measured by regions of interest positioned in thecorticospinal tract at the level of the pons (pons), superior peduncle (SCP), middlecerebellar peduncle (MCP), cerebellar cortex (CeC), cerebral cortex (CC), and cerebellarvermis (CV) white matter;3) Plasma alpha-synapses was extracted with ELISAmethod.Used polymerase chain reaction, agarose gel electrophoresis, As SARA rating scale in patients with ataxia of illness severity. Results:1)13were positive for SCA12and5were the presymptomatic patients.13were successfully detected by recombinantDNA technology.12were heterozygote,1was homozygote. The patients the CAG-repeatenumbers were48-54; The presymptomatic patients the CAG-repeate numbers were49-52;healthy members were detected: the CAG-repeate numbers were9-16. Patients withSCA12CAG sequence repeat number and SARA score of two variables have positivecorrelation (0.708, P＜0.05);2) Compared with the controls, the ADC was significantlyelevated in the CeC, SCP, CC, and CV regions in SCA12patients. The FA significantlydecreased in the CC region in SCA12patients and the CC and CV regions in SCA12presymptomatic patients. The course of the disease, SARA score, and ADC values in CVshowed highly positive correlations;3) Patients with symptoms before the group andnormal control group, three groups of alpha-synuclein is not identical expression levels(P＜0.05), a group of patients with SCA12concentration has the highest overallaverage.But SCA12patients age, disease course and no correlation betweenalpha-synuclein concentration. Conclusions:1) With the longer the duration, the higherthe number of CAG repeats, the higher SARA scores, ataxia patients have more seriousillness.48CAG repeats of SCA12are all the shortest known causative expanded alleles inthe SCA12gene reported to date. The characteristics of Uygur type SCA12genemutation were analyzed, which has important significance of this kind ofdisease, etiology,treatment of accurate classification, prenatal diagnosis;2) SCA12pedigree patientsexhibited microstructural damage in the brain white matter. The damage in white matterfiber may first occur in the CC and CV regions in SCA12presymptomatic patients. TheADC values in the CV region could reflect ataxia and cognitive disorder severity inSCA12patients;3) SCA12patients have abnormal alpha-synuclein aggregation, SCA12patients abnormal α-synuclein aggregates may have a common basis of the incidence andonset of Parkinson’s disease. Detection with Parkinson symptoms in patients with SCA12alpha synuclein may be a biologicalindex as the evaluation of the severity of the diseasesensitive.