Identification of Copy Number Variants in a Southern Chinese Cohort of Patients with Congenital Scoliosis.

Congenital scoliosis (CS) is a lateral curvature of the spine resulting from congenital vertebral malformations (CVMs) and affects 0.5-1/1000 live births. The copy number variant (CNV) at chromosome 16p11.2 has been implicated in CVMs and recent studies identified a compound heterozygosity of 16p11.2 microdeletion and variant/haplotype causing CS in multiple cohorts, which explains about 5-10% of the affected cases. Here, we studied the genetic etiology of CS by analyzing CNVs in a cohort of 67 patients with congenital hemivertebrae and 125 family controls. We employed both candidate gene and family-based approaches to filter CNVs called from whole exome sequencing data. This identified 12 CNVs in four scoliosis-associated genes (, , , and ) as well as eight recessive and 64 novel rare CNVs in 15 additional genes. Some candidates, such as , , , and , have been found to be associated with syndromes with scoliosis or implicated in bone/spine development. In particular, the mutant mouse showed spinal deformities. Our findings suggest that, in addition to the 16p11.2 microdeletion, other CNVs are potentially important in predisposing to CS.