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DOI: 10.1055/s-2008-1065355
© Georg Thieme Verlag KG Stuttgart · New York
Variable Phenotype Including Leigh Syndrome with a 9185T>C Mutation in the MTATP6 Gene
Publication History
received 16.07.2007
accepted 05.03.2008
Publication Date:
06 May 2008 (online)
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.
Key words
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
Correspondence
A.-M. Childs
Department of Paediatric Neurology
Leeds Teaching Hospitals Trust
B Floor
Clarendon Wing
The General Infirmary at Leeds
Belmont Grove
Leeds
West Yorkshire LS2 9NS
United Kingdom
Phone: +44/113/392 31 13
Fax: +44/113/302 57 31
Email: anne-marie.childs@leedsth.nhs.uk