Abstract
The mitochondrial DNA (mtDNA) point mutation T8993G has been associated with maternally inherited Leigh syndrome (MILS) when very abundant (>95%). MILS patients are usually severely affected and die in early infancy. In 1993, a novel T8993C point mutation was described in a juvenile form of Leigh syndrome (LS) characterized by a less aggressive clinical course. We describe four unrelated T8993C patients who had diverse, relatively mild, clinical manifestations. Polymerase chain reaction-restriction fragment length polymphorphism analysis showed that the heteroplasmic T8993C point mutation was very abundant in several tissues from all four patients (94.2 ± 1.5%) but was less copious in blood from 20 maternal relatives. ATP production in mitochondria isolated from skin fibroblasts in three patients was normal, whereas in one patient it was decreased to 20-35% of controls. These findings suggest that the T8993C mutation is less severe than the more common T8993G mutation.
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Abbreviations
- mtDNA:
-
mitochondrial DNA
- MILS:
-
maternally inherited Leigh syndrome
- T8993G or T8993C:
-
T-to-G or T-to-C mutations at nucleotide 8993 in the mtDNA
- LS:
-
Leigh syndrome
- COX:
-
cytochrome c oxidase
- PDHC:
-
pyruvate dehydrogenase complex
- NARP:
-
neurogenicm uscle weakness, ataxia, retinitisp igmentosa
- MRI:
-
magnetic resonance imaging
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Supported in part by program project PO1 HD32062 from the National Institute of Child Health and Human Development (NICHD), by grants from the Muscular Dystrophy Association, and the Colleen Giblin Charitable Foundation. F.M.S. is supported by a scholarship from Telethon-Italia. M.E.V.-M. is supported by a grant from Unidad de Investigación en Genetica Humana, Centro Médico Nacional IMSS, Mexico, DF.
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Santorelli, F., Mak, SC., Vazquez-Memije, M. et al. Clinical Heterogeneity Associated with the Mitochondrial DNA T8993C Point Mutation. Pediatr Res 39, 914–917 (1996). https://doi.org/10.1203/00006450-199605000-00028
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DOI: https://doi.org/10.1203/00006450-199605000-00028
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