Investigation of genetic etiology in familial multiple sclerosis patients

Objective: Multiple sclerosis (MS) is a neuroinflammatory, neurodegenerative chronic disease of the central nervous system (CNS) affecting mostly young adults. MS occurs in genetically predisposed individuals as a result of interaction with environmental factors. Common variations that have been shown to be associated with MS can cumulatively explain about half of MS heritability. Low frequency variations are known to increase the risk of MS. In this study, we aim to identify genes and pathways involved in the pathogenesis of MS. For this purpose, rare variations in genes involved in pathways known to be associated with the etiopathogenesis of MS were examined by whole exome sequencing (WES) in families with 2 or more MS cases, at least one of which had childhood onset. It was aimed to identify possible pathways that may be associated with the disease by performing pathway analysis with rare common variations identified in each family. Materials and Methods: Five patients with childhood-onset multiple sclerosis (POMS) who had a first, second or third degree relative with MS and their closest relative with MS were included in the study. Genomic DNA was extracted from peripheral blood obtained from these patients. Whole exome sequencing was performed from the DNA samples. The sequences were made suitable for analysis with bioinformatics programs and analyses were performed. Results: As a result of the analyses, 53 different variations common among individuals in 5 families and thought to be associated with MS were identified. The genotype-phenotype correlations among these variations were discussed. Conclusion: Although WES analysis alone is not a sufficient evaluation method for MS, which is a multifactorial and polygenic disease, it has been revealed that it is important to exclude rare hereditary diseases included in the differential diagnosis of MS and to identify candidate genes associated with MS.