title: A 7.5-Mb duplication at chromosome 11q21-11q22.3 is associated with a novel spastic ataxia syndrome.
abstract: BACKGROUND
  The autosomal dominant spinocerebellar ataxias are most commonly caused by nucleotide repeat expansions followed by base-pair changes in functionally important genes. Structural variation has recently been shown to underlie spinocerebellar ataxia types 15 and 20.
  
  
  METHODS
  We applied single-nucleotide polymorphism (SNP) genotyping to determine whether structural variation causes spinocerebellar ataxia in a family from France.
  
  
  RESULTS
  We identified an approximately 7.5-megabasepair duplication on chromosome 11q21-11q22.3 that segregates with disease. This duplication contains an estimated 44 genes. Duplications at this locus were not found in control individuals.
  
  
  CONCLUSIONS
  We have identified a new spastic ataxia syndrome caused by a genomic duplication, which we have denoted as spinocerebellar ataxia type 39. Finding additional families with this phenotype will be important to identify the genetic lesion underlying disease.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Molecular Neuroscience and Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Joyce
authors.initials: J
authors.lastname: van de Leemput
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Sampath
authors.initials: S
authors.lastname: Arepalli
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Reza
authors.initials: R
authors.lastname: Zonozi
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005602:France; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009128:Muscle Spasticity / Q000235:genetics*; D009896:Optic Atrophy / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D014314:Trisomy
keywords: SCA39; genomic duplications; spinocerebellar ataxia; structural variation; whole-genome genotyping