Study On The Clinical Features And Genetic Mutation Of Spinocerebellar Ataxia Type 1 From A Kazakh Family

Objective: To investigate the CAG trinucleotide repeates expansion in ATXN1 gene and clinical features of the SCA1 from the Kazak nationality in Xinjiang.To discuss whether the clinical and genetic characteristics of SCA1 in Kazakh families are consistent with those reported in China and outside the China.Methods: According to Harding standard,collected a Kazakh family with diagnosed of SCAs,and drawn the family tree by investigation.9suspected patients and 33 "healthy" family members were assessed with detailed neurological examination,ICARS?MMSE?MOCA and other scales.The mutations of ATXN1 gene amplification of CAG trinucleotide were detected with the Polymerase chain reaction(PCR)? agarose gel electrophoresis ? Target fragment retrieve and cloning sequencing.To detect the ATXN1 gene in 60 Kazakh normal individualities.Used SPSS Statistics23.0 to make a statistical analysis.Results: We detect 9 patients and 10 presymptomatic patients among 42 family members.The main clinical manifestations of SCA1 include walking instability and dysarthria,nd the progress of the disease was slow.The CAG repeat number of abnormal allele of ATXN1 was 41-47 times in 5 patients,with an average of(44.00±2.23)and no CAT insertion in the middle;the number of normal allele CAG repeats was24 to 27,respectively(26.20±1.30).At the same time,there were 2 CAT insertions;4 cases of pre-symptomatic patients had abnormal CAG repeats of40 to 43 times,with an average of(41.75±1.26),with no CAT insertion;the normal allele CAG repeats were 26 to 29 times,average(27.50±1.73)times,and there were 2 CAT insertions.The number of CAG repeats in 23 healthyfamily members was 17 to 30,mean(25.26 ±2.90),28 is the most common frequency is about 21.74%;the sequence interruption by CAT was 0 to 4,2 is the most common frequency is about 30.43%.In 60 healthy controls,the number of CAG repeats was 12 to 30,the average number was(25.87 ±2.61).27 was the most common frequency about 30.00%.the sequence interruption by CAT was 0 to 5,2 is the most common frequency is about 40.00%.Conclusion: 1.The first and early clinical features of SCA1 patients are gait abnormalities,dysarthria and ataxia,the symptoms may involve multiple systems.2.The frequency of abnormal allel CAG repeats in Kazakh patients was all within the abnormal range,and without CAT interruption.26 and 27 was the most common frequency,with 2 CAT interruptions.This is the first time in China to study the ATXN1 gene of Kazakh patients.It is of great significance to explore the etiology,diagnosis and treatment of the disease.3.In the domestic,we first report the CAT interruptions in the sequence of continues CAG repeat numbers,and the interruption of CAT plays a stable role in the protection of ATXN1 gene.