title: Are copy number variants associated with adolescent idiopathic scoliosis?
abstract: BACKGROUND
  Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder that causes spinal deformity in approximately 3% of the population. Candidate gene, linkage, and genome-wide association studies have sought to identify genetic variation that predisposes individuals to AIS, but the genetic basis remains unclear. Copy number variants are associated with several isolated skeletal phenotypes, but their role in AIS, to our knowledge, has not been assessed.
  
  
  OBJECTIVE
  We determined the frequency of recurrent copy number rearrangements, chromosome aneuploidy, and rare copy number variants in patients with AIS.
  
  
  METHODS
  Between January 2010 and August 2014, we evaluated 150 patients with isolated AIS and spinal curvatures measuring 10° or greater, and 148 agreed to participate. Genomic copy number analysis was performed on patients and 1079 control subjects using the Affymetrix(®) Genome-wide Human SNP Array 6.0. After removing poor quality samples, 143 (97%) patients with AIS were evaluated for copy number variation.
  
  
  RESULTS
  We identified a duplication of chromosome 1q21.1 in 2.1% (N = 3/143) of patients with AIS, which was enriched compared with 0.09% (N = 1/1079) of control subjects (p = 0.0057) and 0.07% (N = 6/8329) of a large published control cohort (p = 0.0004). Other notable findings include trisomy X, which was identified in 1.8% (N = 2/114) of female patients with AIS, and rearrangements of chromosome 15q11.2 and 16p11.2 that previously have been associated with spinal phenotypes. Finally, we report rare copy number variants that will be useful in future studies investigating candidate genes for AIS.
  
  
  CONCLUSIONS
  Copy number variation and chromosomal aneuploidy may contribute to the pathogenesis of adolescent idiopathic scoliosis.
  
  
  CONCLUSIONS
  Chromosomal microarray may reveal clinically useful abnormalities in some patients with AIS.
authors.affiliation: Department of Genetics, Washington University School of Medicine, 660 S Euclid Ave, Box 8111, St. Louis, MO, 63110, USA.
authors.forename: Jillian G
authors.initials: JG
authors.lastname: Buchan
authors.forename: David M
authors.initials: DM
authors.lastname: Alvarado
authors.forename: Gabe
authors.initials: G
authors.lastname: Haller
authors.forename: Hyuliya
authors.initials: H
authors.lastname: Aferol
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Miller
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dobbs
authors.forename: Christina A
authors.initials: CA
authors.lastname: Gurnett
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000782:Aneuploidy; D016022:Case-Control Studies; D002877:Chromosomes, Human; D041321:Chromosomes, Human, X / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012600:Scoliosis / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D012729:Sex Chromosome Aberrations; D058533:Sex Chromosome Disorders of Sex Development / Q000235:genetics; D014314:Trisomy / Q000235:genetics