Related Experiment Videos
Clinical correlation of mitochondrial DNA heteroplasmy and Leber's hereditary optic neuropathy
1Department of Ophthalmology, Kagoshima University Faculty of Medicine, Japan.
Abstract:
Mitochondrial DNA (mtDNA) was studied in a Japanese family with two male siblings who were affected with Leber's hereditary optic neuropathy. The polymerase chain reaction (PCR) products of blood mtDNA from the affected siblings, the obligate carrier mother and a possible carrier sister showed abnormal restriction sites for endonucleases SfaNI and Mae III that were compatible with the Wallace mutation at nucleotide position 11,778 base pair of mtDNA, whereas PCR products from the father and controls had normal restriction sites. In addition to the mutant mtDNA, these family members had normal mtDNA that was revealed more obviously in Mae III-digested samples, indicating heteroplasmy consisting of a mixture of mutant and normal mtDNA. The affected siblings showed a marked difference in visual outcome during the 6-year follow-up, and the severity of optic nerve involvement appeared to be correlated with the relative proportion of mutant mtDNA.
Insights
Leber's hereditary optic neuropathy (LHON) in a Japanese family was linked to the Wallace mutation in mitochondrial DNA (mtDNA). The proportion of mutant mtDNA correlated with disease severity in affected siblings.
Area of Science:
- Genetics
- Neurology
- Ophthalmology
Background:
- Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy.
- Mitochondrial DNA (mtDNA) mutations are the primary cause of LHON.
- The Wallace mutation at np 11,778 is a common cause of LHON.
Purpose of the Study:
- To investigate the genetic basis of LHON in a Japanese family.
- To identify the specific mtDNA mutation responsible for LHON in the affected siblings.
- To explore the relationship between heteroplasmy and disease severity.
Main Methods:
- Mitochondrial DNA (mtDNA) was extracted from blood samples of family members and controls.
- Polymerase chain reaction (PCR) was used to amplify specific mtDNA regions.
- Restriction fragment length polymorphism (RFLP) analysis with SfaNI and Mae III endonucleases was performed to detect the Wallace mutation.
- Heteroplasmy levels were assessed based on RFLP results.
Main Results:
- Affected siblings and carrier females carried the Wallace mutation (np 11,778) in their mtDNA.
- Normal mtDNA was also detected in affected individuals, indicating heteroplasmy.
- The proportion of mutant mtDNA varied among family members.
- A correlation was observed between the level of mutant mtDNA and the severity of optic nerve involvement in affected siblings.
Conclusions:
- The Wallace mutation in mtDNA is associated with Leber's hereditary optic neuropathy in this Japanese family.
- Heteroplasmy, a mixture of mutant and normal mtDNA, is present in affected individuals and carriers.
- The level of mutant mtDNA heteroplasmy appears to influence the clinical presentation and severity of LHON.