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Clinical Orthopaedics and Related Research®
Published in: Clinical Orthopaedics and Related Research® 10/2014

01-10-2014 | Basic Research

Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?

Authors: Jillian G. Buchan, MS, David M. Alvarado, PhD, Gabe Haller, PhD, Hyuliya Aferol, BS, Nancy H. Miller, MD, Matthew B. Dobbs, MD, Christina A. Gurnett, MD, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 10/2014

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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.

Questions/Purposes

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.

Clinical Relevance

Chromosomal microarray may reveal clinically useful abnormalities in some patients with AIS.
Appendix
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Metadata
Title
Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?
Authors
Jillian G. Buchan, MS
David M. Alvarado, PhD
Gabe Haller, PhD
Hyuliya Aferol, BS
Nancy H. Miller, MD
Matthew B. Dobbs, MD
Christina A. Gurnett, MD, PhD
Publication date
01-10-2014
Publisher
Springer US
Published in
Clinical Orthopaedics and Related Research® / Issue 10/2014
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-014-3766-8

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