title: A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23.
abstract: BACKGROUND
  The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. To date, 14 autosomal recessive HSP loci have been mapped.
  
  
  METHODS
  We have identified a large consanguineous Omani family in which an autosomal recessive form of HSP is segregating. The age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. To map the chromosomal location of the causative gene we undertook 250K gene chip SNP analyses of all affected individuals assuming that a founder mutation was responsible.
  
  
  RESULTS
  All affected individuals shared a 20.4 Mb (3.25 cM) region of homozygosity located on chromosome 16q21-q23.1, defined by SNP markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). Two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A), were sequenced but no disease causing mutations were identified.
  
  
  CONCLUSIONS
  We have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (HSP) (SPG35) and defined its clinical presentation.
authors.affiliation: Department of Medical Genetics, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Dick
authors.forename: R
authors.initials: R
authors.lastname: Al-Mjeni
authors.forename: W
authors.initials: W
authors.lastname: Baskir
authors.forename: R
authors.initials: R
authors.lastname: Koul
authors.forename: M A
authors.initials: MA
authors.lastname: Simpson
authors.forename: M A
authors.initials: MA
authors.lastname: Patton
authors.forename: S
authors.initials: S
authors.lastname: Raeburn
authors.forename: A H
authors.initials: AH
authors.lastname: Crosby
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009850:Oman; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D005819:Genetic Markers; D009124:Muscle Proteins