Analysis Of Clinical Features And Gene Mutation Of Achado-joseph Disease In Three Families

Purpose: Spinocerebellar ataxia type3(SCA3) was also known asMachado-Joseph Disease(MJD),with obvious characteristics of geneticvariability,clinical heterogeneity and gradually progress. The final diagnosis and typingfor SCA3/MJD depends on gene detection. The purpose is to study the genetic modes,clinical features and MRI changes of the3pedigrees from Dalian, proceed to genedetection for family members, take screening of asymptomatic members in the familyand make a diagnosis before symptoms, in order to deepen the understanding ofDalian region about the SCA3/MJD.Methods: The research object from Dalian, Liaoning Province, is3Han Chinesepopulation family, and clinical diagnoses conformed to Harding standards. We visit andinvestigate the proband families, We drawed the pedigrees of3families, and we madedetailed interrogation and neurological specialist examination to the6patients. We alsoconducted the International Cooperative Ataxia Rating Scale (ICARS) assessment forthe average of scores. After1.5T MRI brain scanning for the probands, we madecomparative analysis through sagittal and horizontal position. We carried on genemutation analysis during patients and asymptomatic family members. Firstly, collectperipheral blood samples from5ml with fasting, extract genomic DNA in the standardmethod of phenol chloroform DNA extraction. Secondly, proceed with the polymerasechain reaction (PCR) and agarose gel electrophoresis. Finally, determine gene types andCAG repeat number based on capillary electrophoresis fragment analysis. Proceed toscore course of disease and ICARS for6patients in the total of3families.Nonparametric rank correlation analysis (Spearman rank correlation analysis) wasaccepted among the correlation course of disease, age of onset and CAG repeat number. The statistics significance level was set at P<0.05.Results: The research was based on6patients, with clinical features of walkinginstability, nystagmus, dysarthria, positive pathological reflex.Two patients have muscletension, one patient with hemifacial spasmand; ICARS scored48points,15points,41points,18points,57points,58points;Brain MRI demonstrated cerebellar,brain stematrophy; It was proved by genetic testing that the6patients were SCA3/MJD-type, andthere were CAG abnormal repeat number with heterozygotes onset. A normal alleleCAG number is20~28times, the abnormal allele CAG repeat number is64~70times.We found CAG repeat expansions mutant in2pre-symptom patients. A normal alleleCAG number is19、21, another allele abnormal expansions of CAG repeat number is66、70times. It was indicated in Spearman rank correlation that the correlationcoefficient for the ICARS score and course of disease was0.53, with tendency ofpositive correlation.Correlation coefficients for the CAG repeat number, course ofdisease and age of onset were-0.318,-0.537, which was negatively related. It was of noobvious statistical significance due to P>0.05.Conclusions:1. There are family in suffer from SCA3/MJD in Dalian. SCA3/MJDis autosomal dominant inheritance, with presences of delayed dominance, geneticheterogeneity, genetic anticipation etc; SCA3/MJD is involved in the cerebellum,brainstem, pyramidal tract.2. ICARS can be a reliable evaluation indicator forSCA3/MJD, and it is possibly positive correlation with course of disease.3. Brain MRIexamination for SCA3/MJD diagnosis presented cerebellum and brainstem atrophy, noabnormal signal, and it was of suggestive for SCA3/MJD diagnosis.4. CAG repeatnumber for SCA3/MJD patients can be negative correlation with course of disease andage of onset.5. Gene detection is the gold standard of accurately diagnosing SCA andtyping, and it is also the main method for screening the presymptom patients, whichwould avoid the babies born with abnormal gene and improve prenatal and postnatalcare.