Date of Award
Doctor of Philosophy (PhD)
Pediatric musculoskeletal disorders are an extremely broad category of diseases that are often inherited. While individually rare, collectively these disorders are common, affecting around 3% of live births in the US. Despite the mounting clinical and molecular evidence for a genetic etiology, the cause for many patients with pediatric musculoskeletal disorders remain largely unknown. Major challenges in rare pediatric diseases include recruiting large numbers of patients and determining the significance and functional impacts of variants associated with disease within individuals or families. Whole exome sequencing (WES) is a powerful tool to identify coding variants that are associated with rare pediatric musculoskeletal disorders. The aims of my dissertation research were to 1) identify genetic variants that are associate with severe adolescent idiopathic scoliosis in a large cohort of more than 1000 unrelated Caucasian cases described in chapter 1, and 2) use zebrafish to investigate the functional effects of variants associated with distal arthrogryposis type 2A, also known as Freeman-Sheldon syndrome, a disorder that is characterized by multiple joint contracture phenotypes including scoliosis described in chapter 2. To accomplish these aims, I performed computational and statistical methods to analyze WES data, and molecular functional genomics screening in zebrafish to characterize and understand the function of gene variants associated with scoliosis phenotype in pediatric musculoskeletal disorders. The knowledge we can gain from this study will not only increase our understanding of the genetic factors contributing in these two pediatric musculoskeletal disorders but most importantly may lead to novel approaches for treatment or preventive strategies.
Chair and Committee
Carlos Cruchaga, Ira Hall, Gabriel Haller, John Rice,
Antunes, Lilian, "Genetics of Pediatric Musculoskeletal Disorders" (2021). Arts & Sciences Electronic Theses and Dissertations. 2358.