title: Genetic analysis of SPG4 and SPG3A genes in a cohort of Chinese patients with hereditary spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP or SPG) is a group of genetically and clinically heterogeneous neurodegenerative disorders. At least 52 different gene loci have been identified so far, involving autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), and maternal inheritance. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes are responsible for about 50% of pure AD-HSP patients. In this study, SPAST and ATL1 mutations were screened in 36 unrelated HSP patients (17 probands with AD family history and 19 sporadic HSP patients) by direct sequencing and multiplex ligation dependent probe amplification (MLPA). We identified 3 micro-mutations and 2 exon deletions in SPAST gene and 2 micro-mutations in ATL1 gene. Four of five micro-mutations were novel and del. ex. 13-15 in SPAST was not reported previously. In this cohort of Chinese patients with spastic paraplegia, SPAST and ATL1 mutations were found in 5 of 17 HSP probands with AD family history and in 2 of 19 sporadic HSP patients. Four novel micro-mutations and one novel exon deletion were identified, which broadened the mutational spectrum of the genes.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China; Department of Neurology, Zhejiang Hospital, Zhejiang 310000, China.
authors.forename: Xingjiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China; Department of Pediatrics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Cen
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China.
authors.forename: Baorong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, China. Electronic address: luoweirock@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010264:Paraplegia / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion; D000074181:Spastin; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human
keywords: Hereditary spastic paraplegia; Micro-mutation; Multiplex ligation dependent probe amplification; Rearrangement mutation; SPG3A; SPG4