Objectives: To find the effect of pathogenic Mitofusin 2mutations, responsible for Charcot-Marie-Tooth hereditary neuropathy type 2A, on protein structure.
Methods: The study was conducted at department of biosciences COMSATS University Islamabad, Sahiwal campus from September 2016to July 2017, and comprised patients with Charcot-Marie-Tooth hereditary neuropathy type 2A who were divided into early-onset severe group A and late-onset mild group B. Bioinformatics and molecular analysis was done to find the changes in the protein structure caused by the mutation. Three mutations were selected in two domains of the gene. These were: p. Arg94Trp, p. His165Arg and p. Thr362Met.
Results: Of the 10 patients, 5(50%) were in each of the two groups. Change in the structure was predicted in the mutated protein at position p. Arg94Trp, and, due to the mutation, an extra alpha helix was formed in the mutated protein.
Conclusion: Change in the structure of protein can be in a critical position that is involved in the mitochondrial fusion process. However, further studies are required to validate and explain the findings.
Key Words: Inherited peripheral neuropathies, CMT2A, MFN2, Functional disability scale, Structural analysis, GTPase domain.