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The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation—implications for diagnosis and management

Lookup NU author(s): Dr Victoria Nesbitt, Dr Robert Pitceathly, Emeritus Professor Doug Turnbull, Professor Robert Taylor, Professor Bobby McFarlandORCiD


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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.

Publication metadata

Author(s): Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R

Publication type: Article

Publication status: Published

Journal: Journal of Neurology, Neurosurgery and Psychiatry

Year: 2013

Volume: 84

Issue: 8

Pages: 936-938

Print publication date: 25/01/2013

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ Group


DOI: 10.1136/jnnp-2012-303528

PubMed id: 23355809


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Funder referenceFunder name
RES/0211/7552Medical Research Council Centre for Translational Research in Neuromuscular Diseases