Neuromuscular disease presentation with three genetic defects involving two genomes

A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle

“…Previous reports have described a dominant- acting mt-tRNA mutation [1] and -as in our index case -a pathogenic mt-tRNA mutation present at low levels in muscle homogenate [26]. Taken together, these unusual clinical cases highlight the value of investigating isolated COX-deficient fibres, particularly when the usual avenues of investigation have previously been explored and excluded.…”

Inherited mitochondrial neuropathies

“…In these cases PNP may be part of a phenotype, which involves several organs [43,119]. In four patients with episodic weakness, encephalopathy, bilateral striatal necrosis, and progressive PNP, homozygosity mapping revealed a pathogenic missense mutation in the SLC25A19 gene [120].…”

Control of mitochondrial integrity in ageing and disease

“…For different mtDNA mutations in muscle, various heteroplasmy threshold effects have been observed, ranging from 67 + 16% [50] to more than 90% [51]. These varying threshold effects are paralleled in other tissues [52][53][54][55] and transmitochondrial cybrid cell lines [56][57][58]. At present, the majority (73%) of reported pathogenic mtDNA mutations are heteroplasmic mutations [17].…”