Related Experiment Videos
Mitochondrial DNA mutations in multiple sclerosis patients with severe optic involvement
U Mayr-Wohlfart1, C Paulus, A Henneberg
1Department of Pathology, University of Ulm, Germany.
Unlabelled:
Preferential maternal transmission in familial cases and the occasional association of multiple sclerosis (MS) and LHON suggests an involvement of mtDNA mutations in the aetiology of MS.
Material & Methods:
DNA obtained from 100 MS patients with pathological alterations in visually evoked potentials and 100 controls, was used for PCR amplification of mtDNA segments. Mutations were identified by restriction enzyme analysis and DNA sequencing.
Results:
Whereas primary LHON mutations are not detected, MS patients show a higher percentage of secondary LHON mutations, usually in a combinatorial manner, than controls. Two neighbouring base pair substitutions that are alleles in a HpaII-polymorphism in the mt tRNA(Thr) gene are significantly more frequent in MS patients than in controls (p = 0.00018).
Conclusion:
Primary LHON mutations are not characteristic for MS with optic involvement, but secondary LHON mutations and two substitutions abolishing a HpaII site in the mt tRNA(Thr) gene may contribute to the aetiology of MS with optic involvement.
Insights
Mitochondrial DNA (mtDNA) mutations, particularly secondary LHON mutations and specific tRNA(Thr) gene substitutions, may play a role in the development of multiple sclerosis (MS) with optic involvement.
Area of Science:
- Neurogenetics
- Ophthalmology
- Mitochondrial Biology
Background:
- Familial cases of multiple sclerosis (MS) show maternal transmission.
- MS is occasionally associated with Leber hereditary optic neuropathy (LHON).
- Mitochondrial DNA (mtDNA) mutations are implicated in MS etiology.
Purpose of the Study:
- Investigate the role of mtDNA mutations in MS.
- Determine if LHON mutations are present in MS patients with visual pathway alterations.
Main Methods:
- PCR amplification of mtDNA segments from 100 MS patients and 100 controls.
- Restriction enzyme analysis and DNA sequencing to identify mutations.
Main Results:
- Primary LHON mutations were not detected in MS patients.
- MS patients exhibited a higher frequency of secondary LHON mutations compared to controls.
- Two specific base pair substitutions in the mt tRNA(Thr) gene were significantly more prevalent in MS patients (p = 0.00018).
Conclusions:
- Primary LHON mutations are not characteristic of MS with optic involvement.
- Secondary LHON mutations and mt tRNA(Thr) gene substitutions may contribute to the etiology of MS with optic involvement.