Abstract
We report a novel, heteroplasmic point mutation in the mitochondrial tRNA for tryptophan at position 5532. The mutation was present in all the tissues studied and segregated with the biochemical defect, with higher levels of mutation present in cytochrome c oxidase-deficient muscle fibres. The patient manifested a neurogastrointestinal syndrome with features including failure to thrive, psychomotor retardation, ophthalmoplegia, sensorineural deafness and encephalopathy together with vomiting, diarrhoea and colitis.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Chinnery PF, Turnbull DM : Mitochondrial DNA and disease. Lancet 1999; 354 (suppl I): 17–21.
Mitomap: MITOMAP: A Human Mitochondrial Genome Database, http://www.mitomap.org, 2003.
Weber K, Wilson JN, Taylor L et al: A new mtDNA mutation showing accumulation with time and restriction to skeletal muscle. Am J Hum Genet 1997; 60: 373–380.
Herrnstadt C, Elson JL, Fahy E et al: Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups. Am J Hum Genet 2002; 70: 1152–1171.
Nelson I, Hanna MG, Alsanjari N, Scaravilli F, Morgan-Hughes JA, Harding AE : A new mitochondrial DNA mutation associated with progressive dementia and chorea: a clinical, pathological, and molecular genetic study. Ann Neurol 1995; 37: 400–403.
Silvestri G, Rana M, DiMuzio A, Uncini A, Tonali P, Servidei S : A late-onset mitochondrial myopathy is associated with a novel mitochondrial DNA (mtDNA) point mutation in the tRNATrp gene. Neuromusc Disord 1998; 8: 291–295.
Santorelli FM, Tanji K, Sano M et al: Maternally inherited encephalopathy associated with a single-base insertion in the mitochondrial tRNATrp gene. Ann Neurol 1997; 42: 256–260.
Tulinius M, Moslemi AR, Darin N et al: Leigh Syndrome with cytochrome-c oxidase deficiency and a single T insertion nt 5537 in the mitochondrial tRNAtrp gene. Neuropediatrics 2003; 34: 87–91.
Bindoff L : Mitochondrial dysfunction and the gastrointestinal system; in Desneulle C, DiMauro S (eds): Mitochondrial disorders: from pathophysiology to acquired disorders, Berlin: Springer; 2002, pp 275–285.
Chinnery PF, Jones S, Sviland L et al: Mitochondrial enteropathy: the primary pathology may not be within the gastrointestinal tract. Gut 2001; 48: 121–124.
Cormier-Daire V, Bonnefont J-P, Rustin P et al: Mitochondrial DNA rearrangements with onset as chronic diarrhea with villous atrophy. J Pediatr 1994; 124: 63–70.
Morris AA, Lamont PJ, Clayton PT : Pearson's syndrome without marrow involvement. Arch Dis Child 1997; 77: 56–57.
Hess J, Burkhard P, Morris M, Lalioti M, Myers P, Hadengue A : Ischaemic colitis due to mitochondrial cytopathy. Lancet 1995; 346: 189–190.
Hirano M, Silvestri G, Blake DM et al: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Neurology 1994; 44: 721–727.
Nishino I, Spinazzola A, Hirano M : Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 1999; 283: 689–692.
Acknowledgements
RWT, ZC-L and DMT acknowledge the continuing support of the Muscular Dystrophy Campaign and The Wellcome Trust.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maniura-Weber, K., Taylor, R., Johnson, M. et al. A novel point mutation in the mitochondrial tRNATrp gene produces a neurogastrointestinal syndrome. Eur J Hum Genet 12, 509–512 (2004). https://doi.org/10.1038/sj.ejhg.5201185
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201185
Keywords
This article is cited by
-
Molecular pathomechanisms and cell-type-specific disease phenotypes of MELAS caused by mutant mitochondrial tRNATrp
Acta Neuropathologica Communications (2015)
-
The tRNAGly T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNAGly, increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential
Molecular and Cellular Biochemistry (2015)
-
Mitochondrial myopathy associated with a novel 5522G>A mutation in the mitochondrial tRNATrp gene
European Journal of Human Genetics (2013)
-
Gastrointestinal and hepatic manifestations of mitochondrial disorders
Journal of Inherited Metabolic Disease (2013)
-
Functional consequences of mitochondrial tRNATrp and tRNAArg mutations causing combined OXPHOS defects
European Journal of Human Genetics (2010)
