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Leber's hereditary optic neuropathy mitochondrial DNA mutations in multiple sclerosis
H Kellar-Wood1, N Robertson, G G Govan
1University of Cambridge Neurology Unit, Addenbrooke's Hospital, United Kingdom.
Annals of Neurology
|July 1, 1994
Summary
Leber's hereditary optic neuropathy mutations in mitochondrial DNA (mtDNA) do not increase risk for typical multiple sclerosis (MS). However, some women with severe optic neuropathy MS may have these mutations.
Area of Science:
- Genetics
- Neurology
- Mitochondrial Biology
Background:
- Multiple sclerosis (MS) is a demyelinating disease with a complex etiology involving genetic and environmental factors.
- Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial DNA (mtDNA) disease primarily affecting the optic nerve.
- A potential link between mtDNA mutations and MS susceptibility has been proposed, particularly in patients presenting with optic neuropathy.
Observation:
- This study investigated the prevalence of specific pathogenic LHON mutations (11778 and 3460) and a suggested pathogenic variant (13708) in the mtDNA of 307 unrelated multiple sclerosis patients.
- The study also examined 129 healthy control subjects for comparison.
- A subgroup of 20 MS patients with prominent and early optic nerve involvement was specifically analyzed.
Findings:
- Neither of the primary pathogenic LHON mutations (11778, 3460) was found in the unselected MS patient cohort.
- The mtDNA base change at position 13708 occurred with similar frequency in both MS patients and healthy controls.
- Three MS patients with severe optic nerve involvement (one with 11778, two with 3460 mutations) were identified; all were female.
Implications:
- The common LHON mtDNA mutations do not appear to contribute to genetic susceptibility in the general multiple sclerosis population.
- A specific subgroup of MS patients, particularly women with severe optic neuropathy, may harbor LHON mutations, warranting consideration for mtDNA analysis.
- While these specific LHON mutations are not a general risk factor, the study leaves open the possibility of other mitochondrial genetic contributions to MS etiology.