Variable Phenotype Including Leigh Syndrome with a 9185T>C Mutation in the MTATP6 Gene

Abstract

We describe 15 members of a Caucasian family with an apparently homoplasmic T→C mutation at nucleotide position 9185 (9185T>C) in the mtDNA encoded MTATP6 (ATPase 6) gene. The clinical phenotype is extremely variable and includes late-onset Leigh syndrome (LS), isolated demyelinating peripheral neuropathy and neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP). Following recent reports of this same mutation in a single case and in a family with late-onset LS and NARP-like features, our paper emphasises the role of MTATP6 in LS and expands the associated clinical phenotype further.

mitochondrial disease - Leigh syndrome - NARP - MTATP6 - 9185T>C

References

• 1 Castagna AE, Addis J, MacInnes RR. et al . Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA.  Am J Med Genet. 2007;  143A 808-816
• 2 Davis PC, Hoffman JC, Braun IF. et al . MR of Leigh's disease (subacute necrotising encephalomyelopathy).  AJNR Am J Neuroradiol. 1987;  8 71-75
• 3 Leigh D. Subacute necrotizing encephalomyelopathy in an infant.  J Neurol Neurosurg Psychiat. 1951;  14 216-221
• 4 Lyons G, Adams RD, Kolodny EH. Early infantile progressive metabolic encephalopathies: clinical problems and diagnostic considerations. Neurology of hereditary metabolic diseases of children. 2nd edn., New York: McGraw-Hill 1996
• 5 Makino M, Horai S, Goto Y, Nonaka I. Mitochondrial DNA mutations in Leigh syndrome and their phylogenetic implications.  J Hum Genet. 2000;  45 69-75
• 6 Moslemi A-R, Darin N, Tulinius M, Oldfors A, Holme E. Two new mutations in the MTATP6 gene associated with Leigh syndrome.  Neuropediatrics. 2005;  36 314-318
• 7 Ogilvie I, Capaldi R. Mutations of the mitochondrially encoded ATPase 6 gene modeled in the ATP synthase of Escherichia coli.  FEBS Lett. 1999;  453 179-182
• 8 Rahman S, Blok RB, Dahl HH. et al . Leigh syndrome: clinical features and biochemical and DNA abnormalities.  Ann Neurol. 1996;  39 343-351
• 9 Santorelli FM, Mak SC, Vazquez-Memije E. et al . Clinical heterogeneity associated with the mitochondrial DNA T8993C point mutation.  Pediatr Res. 1996;  39 914-917
• 10 Tatuch Y, Christodolou J, Feigenbaum A. et al . Heteroplasmic mtDNA mutation (TG) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high.  Am J Hum Genet. 1992;  50 852-858

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