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Acta Neurol Scand. 1995 Nov;92(5):409-15.

Clinical spectrum of the MELAS mutation in a large pedigree.

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Department of Neurology, University of Giessen, Germany.



MELAS is most often due to an mentally transmitted A-G transition mutation of mitochondrial DNA (mtDNA) at position 3243. In this study we report on the clinical spectrum associated with the mutation in the largest family reported so far.


In a family with three MELAS cases we identified 47 persons at risk for the mutation; sufficient data was available on 29. Mitochondrial disease was diagnosed in two of 9 deceased numbers (posthumous molecular analysis in one); 27 surviving family members underwent examination and 25 a molecular analysis of mt DNA from lymphoblasts. Then had a muscle biopsy and two were later autopsied.


All 26 cases investigated by molecular analysis showed the mutation at position 3243. The 18 symptomatic patients without stroke-like episodes had sensorineural hearing loss in 15 cases, diabetes in 6, nephropathy in 7, mild myopathy in 4, cardiomyopathy in 2, cerebellar disease in 4 and mental retardation in 2 cases. Eight carriers were asymptomatic. Autopsy showed > 80% mutant mt DNA in all tissues except blood (20%) examined in a MELAS patients, but < 20 mutant mt DNA in all tissues except lever (40%) and kidney (70%) in a patient with hepatopathy, renal failure and diabetes. Histologic and biochemical studies of muscle biopsy were often non-informative.


The mutation of mt DNA at position 3243 causes a multisystem disorder with a variable phenotype due to heteroplasmy. Most carriers are oligosymptomatic with hearing loss and a variety of neurological and internal medical symptoms. Diabetes, cardiomyopathy and renal disease, which is newly reported here for this mutation, are frequent. The blood test is a reliable screening tool in affected families, but is of prognostic value only combined with examination of other tissues.

[Indexed for MEDLINE]

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