The Investigating Study Of Clinical Characters And Genetic Identification In Hereditary Ataxia Patients

Objective: The aim of this study is,by means of thoroughly collected clinical history and physical examination,to determine the best molecular methods for the affected individuals.Furthermore,to explore the correlation between phenotype and genotype.Moreover,based on phenotype,to predict the probability of illness.In addition,to discovery the variables identified among generations,afford better eugenics for spinocerebellar ataxias(SCAs).Finally,to provide a theoretical basis for the development of therapeutic methods and therapeutic drugs.Methods: One inherent ataxia family members were enrolled in this study.Thoroughly clinical information was achieved for each participants.ICAR(International Cooperative Ataxia Rating Scale),SARA(Scale for the assessment and rating of ataxia),INAS(Inventory of Non-Ataxia Signs),MMSE(mini-mental state examination)were obtained.Routine laboratory examinations were done for each person.1.5T MRI was performed on the proband to recorded alterations between baseline and two-years follow-up.Molecular tests were performed in some individuals,some of them were father-son pairs.WES(whole exome sequencing),SNP Array(single nucleotide polymorphism Array)and FA(fragment analysis)were applied to some volunteers of this pedigree.Results:1.Clinical features: Based on thoroughly collected clinical information,this pedigree was transmitted in an autosomal dominant inheritance pattern,which was clinically defined as SCAs.Clinically,cerebellar-related ataxia was the predominant symptom of the affected individuals.In addition,except for cerebellar-related symptoms,hyperreflexia,dysphagia was obtained.The average age at onset(AO)was 44 years old.No clear evidence showed that there was anticipation among generations.Routine laboratory examinations were nothing significant.Hot cross bun sign(HCBS)and OPCA(olivopontocerebellar atrophy)was observed in the proband.2.Molecular tests: First-time multiple-nucleotide repeat panel was negative because of the CAT interruption in total CAG trinucleotide repeat.WES and SNP Array were negative when performed afterwards.Finally,reevaluated multiple-nucleotide repeat panel was approached,and while a positive result was obtained for the same patient.No CAT interruption was found in this test.To ensure the result,we performed FA and positive results found for the affected individuals and negative results for the unaffected individuals.For the affected individuals,the length of pure CAG repeat were range from 40 to 44,within the boundary length for pathological SCA1.3.Relationship between phenotype and genotype With regard to the phenotype,the mean AO was 44 years old without clear evidence showed anticipation;the chief findings were cerebellar-ataxia,and then pyramid symptoms.With regard to genotype,SCA1 with boundary length of CAG repeat was certified via fragments analysis.The length of CAG repeat may attribute to atypical clinical features of the affected individuals.Conclusions: This pedigree was defined as SCA1 family,both in clinical and genetical.SCAs are a group of highly heterogeneous diseases,thorough clinical information is needed for further evaluation of disease and suitable methods needed to define genetic characters.CAT interruption is extremely critical for CAG trinucleotide repeat diseases,especially when the length of TR is right at the boundary of the pathogenic threshold.