G.P.187: MTO1 mutation in type 2 fiber lipid storage myopathy

Abstract

Disorders of muscle lipid metabolism are due to endocellular triglyceride degradation, carnitine or long-chain fatty acids mitochondrial transport, or fatty acid B-oxidation. MTO1 is a nuclear gene encoding mitochondrial enzyme for post-transcriptional mitochondrial tRNAs modification. We investigated a cohort of 40 cases which pathologically diagnosed as lipid storage myopathy. Whole exome sequencing was performed in genomic DNA from 15 patients, candidate mutations were confirmed by Sanger sequencing. MTO1 gene was sequenced in the remaining 25 cases by Sanger method. One patient carried a compound heterozygous mutation of c.187_188insG:Leu63Argfs*16 and C. 188 T > G:Leu63Arg in MTO1 gene. This patient is a 15-year-old male with cardiomyopathy (Wolff-Parkinson-White syndrome) and lactic acidosis. Interestingly, lipid droplets were increased in size and number predominantly in type 2 fibers while the other cases had lipid storage in type 1. Immunohistochemical and histochemical analysis revealed defects in complex IV especially in type 2 fibers. Our finding of MTO1 mutation in a case with cardiomyopathy and lactic acidosis is in agreement with clinical phenotype of other reported patients with the same gene mutation. The interesting aspect of the current study is muscle lipid accumulation especially in type 2 fibers.