Gene Diagnosis And Clinical Characteristics Research Of Spinocerebellar Ataxia Type3/Machado-joseph Disease In Yunnan Province

ObjectivesTo understand the general characteristics of SCA3/MJD in Yunnan Province, analysis the relationships between CAG repeats and the clinical manifestations of SCA3/MJD patients,preliminary understanding the clinical variation characteristics of SCA3/MJD to provide more basis for clinical diagnosis.MethodsCollected15Spinocerebellar Ataxia patients or presymptomatic cases diagnosed by our department from2011to2013as research subjects,33normal volunteers with no blood relationships as controls. Gathered5millilitres peripheral blood finished DNA extraction, PCR and gene sequencing after gaining signed informed consent of all research subjects, while simultaneously collecting clinical data and completed ICARS and SARA scores. Analysis of each families’clinical characteristics and gene sequencing results. The mean was determined via independent samples T-test, correlation of (CAG)n repeats and onset age via Pearson correlation, test of significance standard for P(2-tailed)<0.05, all statistical analyses carried out using SPSS17.0statistical software.Results(1) Family1displayed two totally different forms:one giving priority to spastic paraplegia, the other more typical clinical manifestations of Spinocerebellar Ataxia. Specific reasons for processes that contribute to this effect are unclear.(2)15families’samples gene sequencing conformed to the SCA3/MJD change. Of these,33cases of (CAG)n repeat control samples are normal. One case of CAG repeats has a pre-mutation (15/46), occasional quaking, kneeling down the two knees in walking and hyperreflexia. One case of CAG repeats manifests di-allele mutations (46/77) who the CAG repeats with parental genetic mutation characteristics at the same time,compared with other members in the line of family his onset age is obviously earlier and the clinical conditions were more severe, clinical course faster progression.(3) Patients’disease progression rate is positively correlated with CAG repeat number, di-allele mutations made the disease worse, and accelerate clinical course progression.(4) This study demonstrates once again the SCA3/MJD with spastic paraplegia clinical variant.Conclusions(1) SCA3/MJD is a mainly subtype of Spinocerebellar Ataxias (SCAs) in Yunnan Province, the incidence of SCA3/MJD18.97%;(2)Yunnan Province SCA3/MJD alleles genes exist with incomplete penetrance mutation (15/46), while di-allele mutations (46/77) made the disease worse and accelerate clinical course progression;(3) A family can have completely different clinical manifestations:CAG repeats only partly explain SCA3/MJD clinical manifestations, and the SCA3/MJD phenotype is a consequence of multiple causal factors;(4) Spinocerebellar ataxia type3(SCA3) can be characterized by obvious hereditary spastic paraplegia with no evident ataxia symptoms.(5) SCA3/MJD mutation gene carriers clearly show a certain degree of early clinical nervous system damage...