A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients
- 16 January 2001
- journal article
- case report
- Published by Wiley in Annals of Neurology
- Vol. 49 (1) , 106-110
- https://doi.org/10.1002/1531-8249(200101)49:1<106::aid-ana16>3.0.co;2-t
Abstract
We identified a novel heteroplasmic mutation in the mitochodrial DNA gene encoding the ND5 subunit of complex I. This mutation (13514A→G) hits the same codon affected by a previously reported mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS)‐associated mutation (13513G→A), but the amino acid replacement is different (D393G vs D393N). The 13514A→G mutation was found in two unrelated MELAS‐like patients. However, in contrast to typical MELAS, lactic acidosis was absent or mild and the muscle biopsy was morphologically normal. Strongly positive correlation between the percentage of heteroplasmy and defective activity of complex I was found in cybrids. We found an additional 13513G→A‐positive case, affected by a progressive mitochondrial encephalomyopathy. Our results clearly demonstrate that the amino acid position D393 is crucial for the function of complex I. Search for D393 mutations should be part of the routine screening for mitochondrial disorders. Ann Neurol 2001;49:106–110Keywords
This publication has 11 references indexed in Scilit:
- The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELASAnnals of Neurology, 1999
- A novel mutation (8342G→A) in the mitochondrial tRNALys gene associated with progressive external ophthalmoplegia and myoclonusNeuromuscular Disorders, 1999
- Identification of a Novel Mutation in the mtDNA ND5 Gene Associated with MELASBiochemical and Biophysical Research Communications, 1997
- The molecular basis and clinical characteristics of Maternally Inherited Diabetes and Deafness (MIDD), a recently recognized diabetic subtypeExperimental and Clinical Endocrinology & Diabetes, 1996
- Clinical spectrum of the MELAS mutation in a large pedigreeActa Neurologica Scandinavica, 1995
- Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNAZeitschrift für Neurologie, 1995
- MELAS: Clinical features, biochemistry, and molecular geneticsAnnals of Neurology, 1992
- A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathiesNature, 1990
- Human Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by ComplementationScience, 1989
- Sequence and organization of the human mitochondrial genomeNature, 1981