Myopathy Diagnosis Improved by New Gene Mutation

A new gene mutation has been discovered which will help doctors give a more accurate diagnosis of a particular type of brain and muscle disease in children.

Mitochondrial myopathy causes muscle weakness, movement problems, and learning difficulties, and for the first time, mutations in a particular gene have been linked to myopathy and this discovery gives a better understanding of the genetic causes of the condition.


An international team of scientists led by those at the St. James's University Hospital (Leeds, UK) studied a cohort of subjects who presented in childhood with a distinctive clinical phenotype comprising early-onset proximal muscle weakness with a static course and moderately to grossly elevated serum creatine kinase levels accompanied by learning difficulties. Muscle biopsies were available for 6 of 15 affected individuals. All showed myopathic features, with diffuse variation in fiber size, increased frequency of internal and central nuclei and clusters of regenerating fibers, without pronounced fibrosis or fatty infiltration.

The investigator identified two mutations in the mitochondrial calcium uptake 1 (MICU1) gene using a technique called exome sequencing which is an alternative to whole genome sequencing. They performed homozygosity analysis using a Genome-Wide Human single nucleotide polymorphism (SNP) Array (Affymetrix; Santa Clara, CA, USA). Whole-exome sequencing of one subject identified only one potentially pathogenic variant in the homozygous region, a splice acceptor site mutation, in MICU1. The team found that mutations in the MICU1 gene caused less protein to be produced which led to an increase in calcium in the mitochondria. This resulted in damage to the mitochondria and changes in calcium levels in the rest of the cell.

Eamonn Sheridan, MB ChB, one of the lead authors of the study said, “The results of this study will enable clinicians to give individuals a more precise diagnosis, and information on how the condition might progress, as well as helping families to make better-informed decisions.” Although it is not known precisely how changes in the cell lead to myopathy, the findings will help provide useful information about the causes of myopathy and how to develop future therapies. The study was published on December 15, 2013, in the journal Nature Genetics.

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