A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy.

摘要: Background Hereditary myopathy with lactic acidosis and deficiency of succinate dehydrogenase aconitase are variants a recessive disorder characterised by childhood-onset early fatigue, dyspnoea palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes widespread weakness, metabolic rhabdomyolysis may occur. So far, this has been molecularly defined only in Swedish patients, all homozygous for deep intronic splicing affecting mutation ISCU encoding scaffold protein the assembly iron–sulfur (Fe-S) clusters. A single Scandinavian family was identified different mutation, missense change compound heterozygosity common mutation. aim study to identify genetic defect our proband. Methods next-generation sequencing (NGS) approach carried out an Italian male who presented childhood ptosis, severe muscle weakness exercise intolerance. His slowly progressive, partial recovery between episodes. Patient’s specimens yeast models were investigated. Results Histochemical biochemical analyses biopsy showed multiple defects mitochondrial respiratory chain complexes. We heterozygous p.Gly96Val , which absent DNA from his parents indicating possible de novo dominant effect patient. Patient fibroblasts normal levels few variably affected Fe-S cluster-dependent enzymes. Yeast studies confirmed both pathogenicity dominance Conclusion describe first results phenotype reminiscent previously reported.