title: Mutation and clinical characteristics of autosomal-dominant hereditary spastic paraplegias in China.
abstract: BACKGROUND
  Hereditary spastic paraplegias constitute a heterogeneous group of inherited neurodegenerative disorders. To date, there has been no systematic mutation and clinical analysis for a large group of autosomal-dominant hereditary spastic paraplegias in China.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the mutation frequencies and the clinical phenotypes of Chinese spastic paraplegia patients.
  
  
  METHODS
  Direct sequencing and a multiplex ligation-dependent probe amplification assay were applied to detect the mutations of SPAST and ATL1 in 54 autosomal-dominant hereditary spastic paraplegia probands and 66 isolated cases. Next, mutations in NIPA1, KIF5A, REEP1 and SLC33A1 were detected in the negative patients. Subsets of spastic paraplegia patients were genotyped for the modifying variants. Further, detailed clinical data regarding the genetically diagnosed families were analysed.
  
  
  RESULTS
  Altogether, 27 families were diagnosed as SPG4, 3 as SPG3A and 1 as SPG6. No mutations in KIF5A, REEP1 or SLC33A1 were found; 9 SPAST mutations were novel. There was no p.S44L or p.P45Q variant in SPAST and no p.G563A variant in HSPD1 in either the 120 spastic paraplegia patients or the 500 controls. There was a remarkable clinical difference between the SPG4 and non-SPG4 patients and even between genders among the SPG4 patients. Non-penetrance and remarkable gender difference were observed in some SPG4 and SPG3A families.
  
  
  CONCLUSIONS
  Our data confirm that hereditary spastic paraplegias in China represent a heterogeneous group of genetic neurodegenerative disorders in autosomal-dominant and apparently sporadic forms. Novel genotype-phenotype correlations were established. © 2014 S. Karger AG, Basel.
authors.affiliation: Department of Neurology, Xianga Hospital of Central South University, Changsha, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Luo
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.forename: Zixiong
authors.initials: Z
authors.lastname: Zhan
authors.forename: Yinguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Hu
authors.forename: Xinxin
authors.initials: X
authors.lastname: Liao
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhao
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
mesh_terms: D000328:Adult; D002681:China; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology*