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Genetics and Functional Pathology of Idiopathic Scoliosis

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The Genetics and Development of Scoliosis

Abstract

Idiopathic scoliosis (IS) has been understood to have a familial or genetic component for decades, yet the genetic mechanisms underlying the disorder are still a subject of active investigation. Identification of genes related to this condition has been difficult due to a number of factors, including genetic heterogeneity, phenotypic heterogeneity, and inconsistent exclusion and inclusion criteria for genetic study participants. Discoveries have kept pace with available genetic technologies, with potentially causal genes and regions having been identified by linkage analyses, candidate gene sequencing, genome-wide association studies (GWAS), and next-generation sequencing methods. The genetic associations with IS that have been replicated to date are variants in or near LBX1 and GPR126, as well as rare variants in multiple extracellular matrix genes. Early animal models of IS have included pinealectomized chickens and bipedal rodents, which led to an interest in melatonin signaling dysfunction as a possible cause of IS. Bony fishes have recently emerged as leading models of IS, starting with the curveback mutant guppy line and progressing to the zebrafish, which was more recently used to create a late-onset scoliosis phenotype through mutations in ptk7 and other motile cilia genes. Today, these animal models in combination with modern sequencing technologies provide powerful tools for the IS research community, with immense potential toward the discovery of additional IS candidate genes and pathways. Determining the genetic factors underlying IS may ultimately improve patient care through diagnostic testing and treatments for affected children.

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Acknowledgments

We thank the laboratory of Dr. Brian Ciruna for providing the micro-CT image of the mutant ptk7 zebrafish in Fig. 7.2.

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Authors and Affiliations

  1. Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Elizabeth A. Terhune, Erin E. Baschal & Nancy Hadley Miller

  2. Musculoskeletal Research Center, Children’s Hospital Colorado, Aurora, CO, USA

    Nancy Hadley Miller

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  1. Elizabeth A. Terhune
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Correspondence to Nancy Hadley Miller .

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Editors and Affiliations

  1. School of Life Sciences, Arizona State University, Tempe, Arizona, USA

    Kenro Kusumi

  2. Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, Australia

    Sally L. Dunwoodie

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Terhune, E.A., Baschal, E.E., Miller, N.H. (2018). Genetics and Functional Pathology of Idiopathic Scoliosis. In: Kusumi, K., Dunwoodie, S. (eds) The Genetics and Development of Scoliosis. Springer, Cham. https://doi.org/10.1007/978-3-319-90149-7_7

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