Analysis Of Copy Number Of Exon In Early Stage Parkinson's Disease In Fujian

Objective:To summarize the clinical data of patients in early-onset Parkinson's disease,analyze the changes in exon copy number of patients in EOPD,and explore the application value of MLPA quantitative technology in genetic diagnosis of PD.Methods :To analyze the clinical data of 150 patients with eruptive EOPD who were enrolled in the study,from December 2007 to August 2017 in the Department of Neurology clinics and wards of the First Affiliated Hospital of Fujian Medical University.The MLPA quantitative technique was used to detect the copy number of exons of DJ1 gene,ATP13A2 gene,PINK1 gene,SNCA gene,parkin gene,UCHL1 gene and LRRK2 gene in 150 patients.Direct DNA sequencing was performed in patients with abnormal exon copy numbers.Results:In 150 sporadic EOPD patients,we detected exon copy number variation(6.67%)in 10 patients,and detected exons copy number variation in parkin gene(6.0%)and UCHL1 gene(0.67%).Exon copy number variation of the other 5 genes.The age of onset of copy number variation in patients with exon 10 was 24 to 49 years,mean age of onset(38±7.071),course of disease from 1 to 20 years,average course of disease(5.30±5.755),and UPDRS score(off period)(37.2±13.626).Hoehr-Yahr stage(off period)(1.85±0.973).All patients were slowly onset,8 cases had asymmetric onset(80%),6 cases had resting tremor(60%),all had exercise retardation(100%)and muscle rigidity(100%),and 3 cases had abnormal gait(30%),5 cases of mask face(50%),1 case of tendon reflex hyperactivity(10%),3 cases of switch phenomenon(30%),are effective for levodopa treatment.Among them,exon copy number variation of the parkin gene was detected in 9 cases: 5 cases were parkin gene exon heterozygous deletion mutations: 1 casein gene no.2 heterozygous deletion mutation,2 cases parkin gene 9th exon heterozygosity deletion Mutations,two cases of parkin gene exon 2 and exon 3 heterozygous deletion mutations;one parkin gene no.2 and exon 3 homozygous deletion mutations;one parkin gene no.3 and exon 4 homozygous deletion mutations;1 case of parkin gene 1,2,3,and 4 exon heterozygous repetitive mutations;one parkin gene 2 and 4 exon heterozygous deletion mutation combined with homozygous deletion of exon 3.One case of UCHL1 gene exon 1 heterozygous deletion mutation.In 10 patients with sporadic EOPD,9 exon deletion mutations(90.0%)and 1 exon repeat mutation(10.0%).Among the patients with 10 exon copy number mutations,one gene polymorphism locus was detected,namely the G601 A pure exon 4 mutation of exon 4 of Parkin gene in 16420 patients,which caused Serl67 Asn polymorphism.Conclusion:1.This study shows that the exon rearrangement mutation of parkin gene is the most common in China,and the mutation rate decreases with the age of onset.2.The mutation rate of parkin genes varies in different regions and races.