title: Clinical and genetic analysis of four Taiwanese families with autosomal dominant hereditary spastic paraplegia.
abstract: OBJECTIVE
  Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Defects in the SPG4 and SPG3A genes are the two leading causes of HSPs with autosomal dominant inheritance (AD-HSPs). The purpose of this study was to investigate the clinical features and associated genetic mutations in Taiwanese families with AD-HSP.
  
  
  METHODS
  Four kindreds with AD-HSP were recruited, and clinical data were collected from the affected individuals. Genetic studies were conducted in the following order: sequence analysis of the SPG4 gene (SPAST) exons, multiplex ligation-dependent probe amplification to detect genetic rearrangements in SPAST, and sequence analysis of the SPG3A gene exons.
  
  
  RESULTS
  Four different SPAST mutations were detected, including a novel small deletion, a missense mutation, and two gross deletions involving exon 17. Although all symptomatic cases manifested as uncomplicated phenotypes, considerable intrakindred and interkindred variations in terms of age at onset, rate of progression, and severity of disease were observed.
  
  
  CONCLUSIONS
  Mutation patterns and phenotypic expressivity are heterogeneous in Taiwanese patients with SPG4-related HSP. Genetic rearrangements could be a significant cause of SPG4-related HSP in the Taiwanese population. Assessment of the large deletions that could present in SPAST is warranted when direct sequencing is uninformative.
authors: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Min-Yu
authors: MY
authors: Lan
authors: Ser-Chen
authors: SC
authors: Fu
authors: Yung-Yee
authors: YY
authors: Chang
authors: Yah-Huei
authors: YH
authors: Wu-Chou
authors: Szu-Chia
authors: SC
authors: Lai
authors: Rou-Shyan
authors: RS
authors: Chen
authors: Chin-Song
authors: CS
authors: Lu
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin; D013624:Taiwan; 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