Abstract
Autosomal recessive progressive external ophthalmoplegia (PEO) is one clinical disorder associated with multiple mitochondrial DNA deletions and can be caused by missense mutations in POLG, the gene encoding the mitochondrial DNA polymerase gamma. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is another autosomal recessive disorder associated with PEO and multiple deletions of mitochondrial DNA in skeletal muscle. In several patients this disorder is caused by loss of function mutations in the gene encoding thymidine phosphorylase (TP). We report a recessive family with features of MNGIE but no leukoencephalopathy in which two patients carry three missense mutations in POLG, of which two are novel mutations (N846S and P587L). The third mutation was previously reported as a recessive POLG mutation (T251I). This finding indicates the need for POLG sequencing in patients with features of MNGIE without TP mutations.
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
Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S: An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 1989; 339: 309–311.
Kaukonen J, Juselius JK, Tiranti V et al: Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 2000; 289: 782–785.
Spelbrink JN, Li FY, Tiranti V et al: Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle a, phage T7 gene 4-like protein localized in mitochondria. Nat Genet 2001; 28: 223–231.
Van Goethem G, Dermaut B, Lofgren A, Martin JJ, Van Broeckhoven C: Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet 2001; 28: 211–212.
Lamantea E, Tiranti V, Bordoni A et al: Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann Neurol 2002; 52: 211–219.
Van Goethem G, Martin JJ, Dermaut B et al: Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord 2002; 13: 133–142.
Nishino I, Spinazzola A, Hirano M: Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 1999; 283: 689–692.
Nishino I, Spinazzola A, Papadimitriou A et al: Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol 2000; 47: 792–800.
Vissing J, Ravn K, Danielsen ER et al: Multiple mtDNA deletions with features of MNGIE. Neurology 2002; 59: 926–929.
Alderborn A, Kristofferson A, Hammerling U: Determination of single-nucleotide polymorphisms by real-time pyrophosphate DNA sequencing. Genome Res 2000; 10: 1249–1258.
Hirano M, Silvestri G, Blake DM et al: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. Neurology 1994; 44: 721–727.
Van Goethem G, Martin JJ, Lofgren A et al: Unusual presentation and clinical variability in Belgian pedigrees with progressive external ophthalmoplegia and multiple deletions of mitochondrial DNA. Eur J Neurol 1997; 4: 476–484.
Acknowledgements
This work was in part supported by a grant from the Danish National Research Foundation (504-14). BD is a doctoral fellow of the Fund for Scientific Research-Flanders (FWO-F).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Van Goethem, G., Schwartz, M., Löfgren, A. et al. Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. Eur J Hum Genet 11, 547–549 (2003). https://doi.org/10.1038/sj.ejhg.5201002
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201002
Keywords
This article is cited by
-
Pharmacovariome scanning using whole pharmacogene resequencing coupled with deep computational analysis and machine learning for clinical pharmacogenomics
Human Genomics (2023)
-
Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis
Molecular Neurobiology (2023)
-
The enteric nervous system in gastrointestinal disease etiology
Cellular and Molecular Life Sciences (2021)
-
Mutations in MTHFR and POLG impaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis
Journal of Human Genetics (2020)
-
Infectious stress triggers a POLG-related mitochondrial disease
neurogenetics (2020)
