Genetic Investigation And Clinical Features Of Autosomal Dominant Hereditary Spastic Paraplegia In China

Objective:Hereditary spastic paraplegia?HSP?is a heterogeneous hereditary neurological disease,which can be divided into simple paraplegia and complex paraplegia.So far,more than 70 genes or loci have been associated with HSP,and the disease has autosomal dominant,autosomal recessive,x-linked or mitochondrial maternal inheritance.In recent years,new autosomal dominant mutation sites have been found.Aim:The main purpose of this study was to screen out pathogenic gene mutations in some patients clinically diagnosed as hereditary spastic paraplegia,and to explore the clinical characteristics and pathogenic gene mutation characteristics of HSP patients.Methods:The subjects of this study were 18 patients with hereditary spastic paraplegia clinically diagnosed as hereditary spastic paraplegia who visited the department of neurology of the second affiliated hospital of medical college of Zhejiang university from 2015 to 2017.Peripheral venous blood was collected and genomic DNA was extracted.Targeted sequencing and Sanger sequencing were applied to detect hsp-related genes.The Multiplex Ligation Dependent Probe Amplification?MLPA?technique was used for gene diagnosis.The corresponding genotype-clinical phenotype relationship was also summarized.Results:Eighteen patients were familial HSP,and gene sequencing showed that 12 patients carried gene mutations,including 4 SPAST mutations?c.427G>T,c.1361A>G,c.1495C>T,and c.1728+2delT?,5 ATL1 mutations?c.746₇48delAAC,c.935T>C,c.1243C>T,c.1246C>T,and c.229delA?;Among them,SPAST gene?c.1728+2delT?,ATL1 gene?c.746₇48delAAC,c.935T>c?and REEP1 gene?c.65delG,c.169A>G,c.229delA?were mutated into unknown mutations.Conclusion:In this study,six new mutations of HSP-related genes were discovered by targeted targeted next-generation sequencing,which expanded the gene mutation spectrum of HSP and further proved that targeted next-generation sequencing could improve the diagnostic efficiency of HSP.Moreover,it is also proved that REEP1 mutation is not rare in Chinese autosomal dominant HSP patients.