title: Clinical features and genotype-phenotype correlation analysis in patients withATL1mutations: A literature reanalysis.
abstract: BACKGROUND
  The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders. Approximately 10% of the autosomal dominant (AD) HSPs (ADHSPs) have the spastic paraplegia 3A (SPG3A) genotype which is caused byATL1gene mutations. Currently there are more than 60 reportedATL1gene mutations and the genotype-phenotype correlation remains unclear. The study aims to investigate the genotype-phenotype correlation in SPG3A patients.
  
  
  METHODS
  We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting anATL1gene mutation.
  
  
  RESULTS
  Most HSPs-SPG3A patients exhibited an early age at onset (AAO) of <10 years old, and showed an autosomal dominant pure spastic paraplegia. We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes, with distal atrophy being the most common complicated symptom. The AAO of each mutation group was not statistically significant (P> 0.05). The mutational spectrum associated withATL1gene mutation is wide, and most mutations are missense mutations, but do not involve the functional motif ofATL1gene encoded atlastin-1 protein.
  
  
  CONCLUSIONS
  Our findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients. We also find that exons 4, 7, 8 and 12 are mutation hotspots inATL1gene.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009 China.|Department of Neurology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, 322000 China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Qianfoshan Hospital, Shandong University, Jinan, 16766 China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Liu
keywords: ATL1; Age at onset; Genotype-phenotype correlation; Hereditary spastic paraplegia; Mutation; SPG3A