Title: “The role of tRNA synthetases in neurological and neuromuscular disorders”
Speaker: Professor Rita Horvath, Professor of Neurogenetics, Institute of Human Genetics, Newcastle University
Venue: Rooms B02/B03, SITraN, 385a Glossop Road,
Sheffield S10 2HQ
Nuclear genes in mitochondrial disease
Mitochondrial disorders are a heterogeneous group of rare diseases that result from deficiency in cellular energy production. Our investigations focus on pediatric disorders with combined respiratory chain deficiency of nuclear origin. Combined respiratory chain deficiency is present in approximately 30% of all biochemical defects in infants with mitochondrial disease.
We have recently identified the molecular genetic cause, a homoplasmic mitochondrial tRNA mutation in a puzzling clinical syndrome, initially termed “benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase (COX) deficiency”. While childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions with fatal outcome, this syndrome stands out by showing complete (or almost complete) spontaneous recovery. The exact pathomechanims of this disease is currently being investigated.
We concentrate our studies on two groups of disorders, on deficiencies of mitochondrial translation due to mutations in nuclear genes and coenzyme Q10 deficiency diseases in patients with severe combined respiratory chain deficiencies, where known defects such as mtDNA depletion and mtDNA mutations were excluded. Most of the gene defects in this group of patients remain unknown and there are no effective treatments.
We try to elucidate the frequency and disease characteristics of nuclearencoded mitochondrial translation impairments and coenzyme Q10 deficiencies with the aim to identify new disease genes. The results will provide practical benefits for genetic counselling and treatment of these patients, reveal new insights into the pathomechanism of combined RC deficiency and also allow a first assessment of the currently unknown prevalence of these disorders.
These studies are performed within Professor Patrick F. Chinnery´s group and in collaboration with Professors Turnbull, Taylor and Lightowlers within the Mitochondrial Research Group.