Neuromuscular Disorder As A Chronic Disease And Its Impact On Quality Of Life

Abstract

Numerous diseases are categorized as chronic disorders. These can be related to neurological disorders, movement disorders, respiratory diseases, cancer, autoimmune disorders, andgenetic disorders. Chronic disorders are a prime contribution in deaths occurring below 70 years of age. Functional disability scale was use to measure the hardships associated with disease that indirectly affect the routine life of the sufferers. Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common subtype of inherited peripheral neuropathy characterized by distal muscle weakness, atrophy and sensory loss. CMT1A is caused by the duplication of PMP22 gene on chromosome 17p12 region. However, despite this evident cause, onset age or severity is considerably variable among patients. The exact reason behind these phenotypic heterogeneities is rarely discovered yet, but certain secondary factors are assumed to be involved. Since miRNAs are the key regulators of gene expression, we speculated variants of miRNAs might be the genetic modifiers for CMT1A. This study noticed a common single nucleotide polymorphism (SNP) of miR-149(rs2292832) as a possible candidate. MiR-149 was predicted to target several CMT causing genes including SH3TC2, LITAF, MPZ, and PMP22 by several prediction algorisms.The rs2292832 was located near the 3 end of precursor, the important region for maturation. From the association study for 176 unrelated Korean CMT1A patients, we identified that the TC/CC genotypes of rs2292832 were significantly associated with late onset (onset age ≥20) and mild phenotype (functional disability scale 0-2, CMT neuropathy score 0-10). Therefore, this study suggests that themiR-149SNP has the considerable potential to affect the phenotypic heterogeneity of CMT1A as genetic modifiers.