MITOCHONDRIAL VARIANT m.3243A>G IN MELAS OR DIABETES AND DEAFNESS
The mitochondrial variant m.3243A>G is associated with the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes; Goto et al 1990 Nature 348: 651-653) and the MIDD syndrome (maternally inherited diabetes and deafness; Ballinger et al 1992 Nat Genet 1: 11-15). Additional clinical features associated with the m.3243A>G variant include short stature, cardiomyopathy, myopathy, renal disease, macular dystrophy and gastrointestinal disease (Murphy et al 2008 Diabet Med 25: 383-399). Mitochondrial variants are passed on through the maternal germline, and so all maternal relatives of an individual with MIDD or MELAS are likely to be obligate carriers of the m.3243A>G variant. However the clinical phenotype associated with the m.3243A>G variant may be very heterogeneous, even within the same family s (Nesbitt et al 2013 J Neurol Neurosurg Psychiatry 84: 936-938). Part of this variation in phenotype is due to the amount of heteroplasmy (the mixture of wild-type and mutant mitochondrial DNA in each cell) inherited, the subsequent segregation of mutant mitochondrial DNA in the different tissues and changes in the level of heteroplasmy in different tissues with increasing age.
The laboratory participates in the United Kingdom National External Quality Assessment Service (UK NEQAS) Mitochondrial Diseases scheme.