Quantifying environmental risk factors for multiple sclerosis in discordant monozygotic twins: a case report

Relative contribution of genetic and environmental risk factors in complex disorders is widely explored through discordant identical twins. Multiple sclerosis is a demyelinating disease of the central nervous system in which the interplay of genetic and environmental risk factors define the disease pathogenicity. Robust epidemiological studies in different populations suggested that active levels of serum vitamin D and viral load implicate in MS pathogenicity and severity. In order to refine non-shared components of susceptibility factors in MS, we investigated the role of serum 25-hydroxyvitamin D and viral infection in a pair of identical twins remained discordant for MS during the course of 5 years follow up. Here we report serological finding regarding the viral load and serum 25-hydroxyvitamin D level in a pair of discordant monozygotic twins. Based on our observation, lower levels of serum 25-hydroxyvitamin D and higher anti-viral IgG titre was consistent with the disease statues in the affected sib

Co-occurrence of multiple sclerosis and Thomsen’s myotonia: a report of two cases

Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system in which an abnormal immune system response results in damage to the myelin sheaths surrounding nerves. The etiology of MS remains elusive, although it has been suggested to be influenced by both genetic and environmental factors. Here, we report two exceptional cases of patients affected by both MS and Thomsen’s myotonia. Electromyography and MRI scans confirmed the presence of both diseases in the referred cases. Although the mechanisms underlying the co-occurrence of MS and Thomsen’s disease are unclear, we have endeavored to offer plausible explanations for it

Zinc finger nuclease technology: advances and obstacles in modelling and treating genetic disorders

Zinc finger nucleases (ZFNs) are engineered restriction enzymes designed to target specific DNA sequences within the genome. Assembly of zinc finger DNA-binding domain to a DNA-cleavage domain enables the enzyme machinery to target unique locus in the genome and invoke endogenous DNA repair mechanisms. This machinery offers a versatile approach in allele editing and gene therapy. Here we discuss the architecture of ZFNs and strategies for generating targeted modifications within the genome. We review advances in gene therapy and modelling of the disease using these enzymes and finally, discuss the practical obstacles in using this technology

The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility.

Multiple sclerosis (MS) is the most common neurological disease of the central nervous system affecting young adults. While the etiology of the disease is still unknown, epidemiological and genetics studies have shown a significant inherited component involved in MS pathogenesis. Single nucleotide polymorphisms (SNPs) associated with MS have been recently evaluated by two main groups of high-throughput genotyping analyses: candidate gene approaches and genome-wide association studies (GWAS). Although both types of studies have identified polymorphisms in the human leukocyte antigen (HLA) region as the strongest susceptibility loci for MS, recent investigations have identified a broad spectrum of non-HLA genes prominently associated with MS. This review will focus on recent findings in non-HLA genes as well as their SNPs which have shown high linkage to MS as a genetic-based disorder. Understanding of non-HLA polymorphisms will help elucidate the signalling aberrations involved in MS development and may help to identify novel, personalized approaches to therapy