Clinical orthopaedics and related research · 2014
Are copy number variants associated with adolescent idiopathic scoliosis?
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Buchan Jillian G, Alvarado David M, Haller Gabe, Aferol Hyuliya, Miller Nancy H, Dobbs Matthew B, Gurnett Christina A
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAge FactorsAneuploidyCase-Control StudiesChromosomes, HumanChromosomes, Human, XDNA Copy Number VariationsFemaleGene DosageGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleOligonucleotide Array Sequence AnalysisPhenotypePolymorphism, Single NucleotideRisk FactorsScoliosisSex Chromosome AberrationsSex Chromosome Disorders of Sex DevelopmentTrisomy