Clinical Features,Gene Mutation And Treatment Of Spinocerebellar Ataxias:in Patents Of A Family

[Objective]1. To determinate the clinical features of patients with spinocerebellar ataxias (SCAs), which are from a family inYanyuan county, Sichuan province,China.2.Polmerase chain reaction (PCR) and direct sequencing used to study the frequency of SCAs CAG trinucleotide repeat expansion(CAGn) among the patients in the family with SCAs, and to investigate the relationship between the clinical features and gene mutation.3. The proband of the SCAs family was performed by hunman neural stem cell transplantion for exploratory treatment, to study the clinical feasibility and safety of hunman neural stem cell transplant.[Methods]1. The proband of the SCAs family was found in the Navy General Hospital. According to the Harding standization, the patient was diagnosed as SCAs by clincal manifestation, imaging examination and family history. In order to comprehensively and profoundly understand clinical features of SCAs in the family, neurological examination, Mini-mental state examination (MMSE) and International Cooperative Ataxia Rating Scale(ICARS) was performed to evalue the proband and part of the members from the family, and the pedigree map was draw up.2. Peripheral the vein blood of part of the members was collected, DNA extracted, amplified by PCR and the PCR products were sequenced. Gene mutation about CAG trinucleotide repeate expansion was analysised to reach the final diagnose of asymptomed patients.3.Cells from human fetal cerebellum were expand in vitro and were allowed to differentiate into neurospheres, the latter were implanted into the proband dentate nuclei with stereotactic operation to study the effect and safety of human neural stem cell transplant. [Results]1. All the patients of SCAs were clinically characterized as progressive ataxia, dysarthria and pyramidal signs. The magnetic resonance imaging(MRI) showed atrophy of cerbellum. The SCAs were found in males and females, ages of the patients ranged from5-60years, the mean age was39.7±14.3years,the mean male age was38.1±14.8years, the mean female age was41.3±14.6years,the mean of second generation age was48.2±3.6years,the mean of third generation age was41.1±5.9years,the mean of fourth generation age was12.3±6.4years.seven patient,s scores of ICARS were range from2to52,and the scores of MMSE were range from15to29. Two patients (IV33、IV35)characterized by mild cognitive dysfunction.2. A total of5patient and2presymptomatic individuals were detected from26numbers of4generations in the family. The CAG repeat were expanded to60-78repeats in the ATXN3in SCAs, and60,62repeats in presymptomatic individuals.3. No complications were found after neural stem cell transplant with stereotactic operation in the proband of SCAs family. At6months follow-up, slurred speech and walking instability symptoms improved. It is feasible and effective to transplant the neural stem cells for treatment of SCAs, but the long term effect should be further observed.[Conclusions]Spinocerebellar ataxia type3(SCA3), also known as Machado-Joseph disease (MJD), may be the most common dominantly inherited ataxia in the world. Cerebellar ataxia, progressive external ophthalmoplegia, dysarthria, dysphagia, pyramidal signs, dystonia, rigidity, and distal muscle atrophies are common features of SCA3. The most common MRI finding is pontocerebellar atrophy with a dilated fourth ventricle. The gene diagnosis is more accurate and can be used as diagnostic criteria. Stem cells transplant, a new treatment for neurodegenerative diseases, is still in the stage of clinical trials, but the long term effect should be further observed.