Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population, and is characterized by a three-dimensional deviation of the spinal axis that occurs in the absence of underlying vertebral anomalies or obvious physiological defects. The pathogenesis of scoliosis is poorly understood and despite several evidences suggesting a role of genetics component in the pathogenesis, limited progresses have been accomplished in the identification of the causative genes.
Next generation sequencing (NGS) has revolutionized medical genetics: it is accelerating the research about rare-genetic disease and in the future it will facilitate clinical diagnosis and personalized medicine. Exome sequencing techniques have been proven as useful technique to specifically define IS-associated genetic variations in familial cases of scoliosis.
The aim of the proposed research is to perform a clinical and genetic study in a multigenerational family with several members affected by a severe form of scoliosis. We will study molecular bases of idiopathic scoliosis by using a whole exome sequencing approach on affected family members in order to provide useful information on dysregulated cellular pathway and suggest altered mechanism that may underlie susceptibility also to sporadic condition.
Despite several evidences suggesting a role of genetics component in the pathogenesis of IS, limited progress have been accomplished in the identification of the causative gene/s.
Next generation sequencing (NGS) has revolutionized medical genetics: it is accelerating the research about rare-genetic disease and in the future it will facilitate clinical diagnosis and personalized medicine. Both whole exome sequencing (WES) and whole genome sequencing (WGS) are powerful techniques for the detection of human genetic variation. Because of the complexity and the greater cost of WGS, WES is currently the most used approach for the discovery of disease-causing genes, as to date, about 85% of the disease-causing mutations identified, is located in coding regions of the genome. For this reason, exome sequencing could shed light on the molecular bases of several rare genetic disorders as well as predisposing variants of common diseases and cancers.
Large pedigrees are very useful for the study of molecular bases of Mendelian diseases by using exome sequencing approach as it could be hypothesized that the same causative variant segregates in all affected members. This could help the filtering and prioritization step of candidate variants analyses.
The availability of this multigenerational family with several members affected by IS represents a valuable condition to identify rare genetic variants that contribute to the IS phenotype.
The identification of the molecular bases of the familial idiopathic scoliosis could provide useful information on dysregulated cellular pathway and suggest altered mechanism that may underlie susceptibility also to sporadic scoliosis.