| Autor: |
Terhune EA; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Wethey CI; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Cuevas MT; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Monley AM; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Musculoskeletal Research Center, Children's Hospital Colorado, Aurora, CO 80045, USA., Baschal EE; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Bland MR; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Baschal R; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Musculoskeletal Research Center, Children's Hospital Colorado, Aurora, CO 80045, USA., Trahan GD; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Taylor MRG; Department of Medicine, Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Jones KL; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Cell Biology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA., Hadley Miller N; Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Musculoskeletal Research Center, Children's Hospital Colorado, Aurora, CO 80045, USA. |
| Abstrakt: |
Adolescent idiopathic scoliosis (AIS) is a lateral spinal curvature >10° with rotation that affects 2-3% of healthy children across populations. AIS is known to have a significant genetic component, and despite a handful of risk loci identified in unrelated individuals by GWAS and next-generation sequencing methods, the underlying etiology of the condition remains largely unknown. In this study, we performed exome sequencing of affected individuals within 23 multigenerational families, with the hypothesis that the occurrence of rare, low frequency, disease-causing variants will co-occur in distantly related, affected individuals. Bioinformatic filtering of uncommon, potentially damaging variants shared by all sequenced family members revealed 1448 variants in 1160 genes across the 23 families, with 132 genes shared by two or more families. Ten genes were shared by >4 families, and no genes were shared by all. Gene enrichment analysis showed an enrichment of variants in cytoskeletal and extracellular matrix related processes. These data support a model that AIS is a highly polygenic disease, with few variant-containing genes shared between affected individuals across different family lineages. This work presents a novel resource for further exploration in familial AIS genetic research. |
