An Identification Of The Disease-causing Genes Of A Hereditary Ataxia Family

Background and Objective Inherited ataxias(HA)is a neurodegenerative disease with significant clinical and genetic heterogeneity,with a high mortality and disability rate.The genetic methods mainly include autosomal dominant inheritance,autosomal recessive inheritance,x-linkage inheritance and mitochondrial correlation heredity.Hereditary ataxia is mainly involved in cerebellum,brainstem,spinal cord and related cranial nerve nuclei,and the clinical manifestations mainly include progressive aggravation of ataxia.The disease is usually insidious onset,slow progress,complicated clinical manifestations,varied lesion sites,and different degree of damage.To date,it has been found that there are several types of genetic mutations in inherited ataxia,which help to diagnose complex genetic causes of such diseases.Most of the hereditary ataxia is caused by the repeated amplification of trinucleotides,however,conventional mutations are an important reason for rare and recessive ataxia.Advances in sequencing technology have led to the emergence of these rare ataxia genes in clinical studies.With the development of science and technology,gene diagnosis has become an important diagnostic means of ataxia.Prophase work we have found a clinically rare genetic three generations of the HA system,family system and related family members of patients whole exons group sequencing,and bioinformatics analysis,select relevant candidate genes based on the above results.In this study,Sanger sequencing was performed on the related candidate genes of the autosomal dominant ataxia family,looking for the pathogenic genes of the HA family.Methods1.One case of autosomal dominant ataxia Han family was acquired by the inpatient department of the China-Japan Union Hospital of Jilin University.We conducted a detailed medical history,physical examination,mapping of genetic lineage,MMSE,ICARS test score of the autosomal dominant ataxia Han family,and carried out MRI scans of head in some cases of this family.Fifty healthy people were chosen as the control group2.The family members of patients and related family members of the whole exome sequencing,and bioinformatics analysis,based on the above results,screening out the candidate genes.Sanger sequencing technology was used to detect the genes of blood samples from family members and control group.Result1.The hereditary ataxia family has 3 generations,6 of whom are ill,and 5 existing patients have a clear family history,all of which are characterized by the slow progress of cerebellar ataxia.They were not treated.The pedigree has incidence of each generation,the incidence were male,the second generation of 4 people,the incidence rate was 40%,the third generation of 1 incidence,,and the incidence was 14.3%.The onset age of the 5 cases in the family was between 24 to 30 years old,the average age of oneset was 27.4 ± 2.2 years.The average age of onset in the second generation was 28.3 ± 1.5 years,and in the third generation was 24 years old,the third generation is older than the second generation.The ICARS scores of the 5 survivors were 32,19,21,36,and 10 respectively.The MMSE scores were 29,30,22,28,29 respectively.2.There were 2 cases in the family of 5 patients with head MRI showing cerebellar atrophy.3.In the genetic examination of the family,ALDH5A1 gene was found to have G→A mutation and C→G mutation occurred in CACNA1 C gene,and T→TAA mutation occurred in VLDLR gene.Conclusion1.The mutation site of CACNA1 C found in this autosomal dominant ataxia family is an significant change that leads to ataxia in the family.2.Clinical manifestations,CT and MR imaging changes are important diagnostic criteria for HA,and genetic testing is the gold standard for the diagnosis of HA.