Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?
Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?
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DOI：
10.1007/s11999-014-3766-8
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发表时间：
2014-10-01
影响因子：
4.2
通讯作者：
Gurnett, Christina A.
中科院分区：
文献类型：
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作者：
Buchan, Jillian G.;Alvarado, David M.;Gurnett, Christina A.
青少年特发性脊柱侧凸（AIS）是一种复杂的遗传疾病，大约3%的人口会导致脊柱畸形。候选基因、连锁和全基因组关联研究试图确定个体易患AIS的遗传变异，但遗传基础尚不清楚。拷贝数变异与几种分离的骨骼表型相关，但据我们所知，它们在AIS中的作用尚未得到评估。我们确定了AIS患者中复发性拷贝数重排、染色体非整倍体和罕见拷贝数变异的频率。2010年1月至2014年8月，我们评估了150例孤立性AIS患者，脊柱弯曲度为10A度或更大，其中148人同意参与。使用Affymetrix(A (R)) Genome-wide Human SNP Array 6.0对患者和1079名对照组进行基因组拷贝数分析。在剔除质量差的样本后，对143例（97%）AIS患者的拷贝数变化进行了评估。我们在2.1% （N = 3/143）的AIS患者中发现了染色体1q21.1的重复，与对照组（p = 0.0057）的0.09% （N = 1/1079）和大型已发表的对照队列（p = 0.0004）的0.07% （N = 6/8329）相比，染色体1q21.1的重复更为丰富。其他值得注意的发现包括1.8% （N = 2/114）的AIS女性患者中发现的X三体，以及先前与脊柱表型相关的染色体15q11.2和16p11.2的重排。最后，我们报告了罕见的拷贝数变异，这将有助于未来研究AIS的候选基因。拷贝数变异和染色体非整倍体可能与青少年特发性脊柱侧凸的发病机制有关。染色体微阵列可能揭示一些AIS患者临床上有用的异常。
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.We determined the frequency of recurrent copy number rearrangements, chromosome aneuploidy, and rare copy number variants in patients with AIS.Between January 2010 and August 2014, we evaluated 150 patients with isolated AIS and spinal curvatures measuring 10A degrees or greater, and 148 agreed to participate. Genomic copy number analysis was performed on patients and 1079 control subjects using the Affymetrix(A (R)) Genome-wide Human SNP Array 6.0. After removing poor quality samples, 143 (97%) patients with AIS were evaluated for copy number variation.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.Copy number variation and chromosomal aneuploidy may contribute to the pathogenesis of adolescent idiopathic scoliosis.Chromosomal microarray may reveal clinically useful abnormalities in some patients with AIS.