title: Copy number variation in pediatric multiple sclerosis.
abstract: BACKGROUND
  Pediatric onset multiple sclerosis (MS) accounts for 2-4% of all MS. It is unknown whether the disease shares the same underlying pathophysiology found in adult patients or an extreme early onset phenotype triggered by distinct biological mechanisms. It has been hypothesized that copy number variations (CNVs) may result in extreme early onset diseases because CNVs can have major effects on many genes in large genomic regions.
  
  
  OBJECTIVE
  The objective of the current research was to identify CNVs, with a specific focus on de novo CNVs, potentially causing early onset MS by competitively hybridizing 30 white non-Hispanic pediatric MS patients with each of their parents via comparative genomic hybridization (CGH) analysis on the Agilent 1M CGH array.
  
  
  CONCLUSIONS
  We identified 10 CNVs not overlapping with any CNV regions currently reported in the Database of Genomic Variants (DGV). Fifty-five putatively de novo CNVs were also identified: all but one common in the DGV. We found the single rare CNV was a private variation harboring the SACS gene. SACS mutations cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease. Additional clinical review revealed that the patient with the SACS gene CNV shared some features of both MS and ARSACS.
  
  
  CONCLUSIONS
  This is the first reported study analyzing pediatric MS CNVs. While not yielding causal variation in our initial pediatric dataset, our approach confirmed diagnosis of an ARSACS-like disease in addition to MS in the affected individual, which led to a more complete understanding of the patient's disease course and prognosis.
authors.affiliation: Department of Neurology, University of California at San Francisco, USA. Joseph.McElroy@OSUMC.edu
authors.forename: J P
authors.initials: JP
authors.lastname: McElroy
authors.forename: L B
authors.initials: LB
authors.lastname: Krupp
authors.forename: B A
authors.initials: BA
authors.lastname: Johnson
authors.forename: J L
authors.initials: JL
authors.lastname: McCauley
authors.forename: Z
authors.initials: Z
authors.lastname: Qi
authors.forename: S J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: P A
authors.initials: PA
authors.lastname: Gourraud
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Nathanson
authors.forename: A L
authors.initials: AL
authors.lastname: Belman
authors.forename: S L
authors.initials: SL
authors.lastname: Hauser
authors.forename: E
authors.initials: E
authors.lastname: Waubant
authors.forename: D J
authors.initials: DJ
authors.lastname: Hedges
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009128:Muscle Spasticity / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000151:congenital / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human