title: Clinical heterogeneity and genotype-phenotype correlations in hereditary spastic paraplegia because of Spatacsin mutations (SPG11).
abstract: BACKGROUND
  Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum is a distinct and usually severe form of complex hereditary spastic paraplegia classified as SPG11. Recently mutations on SPG11 gene (KIAA1840), which is localized to chromosome 15q13-q15, were shown to cause the majority of SPG11 cases.
  
  
  METHODS
  We analysed the 40 coding exons of this gene in the probands from eight families with complex ARHSP, four of these families had a thin corpus callosum and two has mild thinning.
  
  
  RESULTS
  Three families were identified with novel mutations in the SPG11 gene. One family was of Asian origin with a homozygous nonsense mutation and had a very severe phenotype but only very mild thinning of the corpus callosum. In the other two English families the parents were unrelated and the mutations were compound heterozygotes. In these two families the phenotype was mild and both probands had a thin corpus callosum.
  
  
  CONCLUSIONS
  Given the probable mechanism of action of the mutations in the Spatacsin gene, we discuss the probable genotype phenotype correlations in these families. This study confirms the frequent occurrence of Spatacsin mutations in complex ARHSP with genotype phenotype effects and exposes the spectrum of clinical heterogeneity in SPG11.
authors: Department of Molecular Neuroscience, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom. C.Paisan-Ruiz@ion.ucl.ac.uk
authors: C
authors: C
authors: Paisan-Ruiz
authors: P
authors: P
authors: Nath
authors: N W
authors: NW
authors: Wood
authors: A
authors: A
authors: Singleton
authors: H
authors: H
authors: Houlden
mesh_terms: D000293:Adolescent; D000328:Adult; D018389:Codon, Nonsense; D003072:Cognition Disorders / Q000235:genetics; D003241:Consanguinity; D003337:Corpus Callosum / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D022821:RNA Splice Sites / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D011506:Proteins; D022821:RNA Splice Sites; C520412:SPG11 protein, human