@article {Nesbitt936, author = {Victoria Nesbitt and Robert D S Pitceathly and Doug M Turnbull and Robert W Taylor and Mary G Sweeney and Ese E Mudanohwo and Shamima Rahman and Michael G Hanna and Robert McFarland}, title = {The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation{\textemdash}implications for diagnosis and management}, volume = {84}, number = {8}, pages = {936--938}, year = {2013}, doi = {10.1136/jnnp-2012-303528}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Population-based studies suggest the m.3243A\>G mutation in MTTL1 is the most common disease-causing mtDNA mutation, with a carrier rate of 1 in 400 people. The m.3243A\>G mutation is associated with several clinical syndromes including mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS), maternally inherited deafness and diabetes (MIDD) and progressive external ophthalmoplegia (PEO). Many patients affected by this mutation exhibit a clinical phenotype that does not fall within accepted criteria for the currently recognised classical mitochondrial syndromes. Methods We have defined the phenotypic spectrum associated with the m.3243A\>G mtDNA mutation in 129 patients, from 83 unrelated families, recruited to the Mitochondrial Disease Patient Cohort Study UK. Results 10\% of patients exhibited a classical MELAS phenotype, 30\% had MIDD, 6\% MELAS/MIDD, 2\% MELAS/chronic PEO (CPEO) and 5\% MIDD/CPEO overlap syndromes. 6\% had PEO and other features of mitochondrial disease not consistent with another recognised syndrome. Isolated sensorineural hearing loss occurred in 3\%. 28\% of patients demonstrated a panoply of clinical features, which were not consistent with any of the classical syndromes associated with the m.3243A\>G mutation. 9\% of individuals harbouring the mutation were clinically asymptomatic. Conclusion Following this study we propose guidelines for screening and for the management of confirmed cases.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/84/8/936}, eprint = {https://jnnp.bmj.com/content/84/8/936.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }