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Case report: A rare variant m.4135T>C in the
Tereza Rákosníková1, Silvie Kelifová1, Hana Štufková1
1Laboratory for Study of Mitochondrial Disorders, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czechia.
Frontiers in Genetics
|June 5, 2023
Summary
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease causing vision loss. A rare MT-ND1 gene variant (m.4135T>C) impairs mitochondrial complex I function, leading to LHON symptoms when combined with external triggers.
Area of Science:
- Genetics
- Mitochondrial Biology
- Ophthalmology
Background:
- Leber hereditary optic neuropathy (LHON) is a primary mitochondrial disease.
- It is characterized by acute visual loss due to retinal ganglion cell degeneration.
Observation:
- A patient presented with a rare heteroplasmic variant in MT-ND1 (m.4135T>C, p.Tyr277His).
- Symptoms included bilateral, painless vision decrease triggered by exercise or heat.
Findings:
- The Tyr277His substitution negligibly affected respiratory chain complex I (CI) levels but significantly disturbed supercomplex formation and activity.
- Mitochondrial CI assembly was intact, but the m.4135T>C variant impaired its function, potentially by stabilizing an inactive form.
Implications:
- This variant, in conjunction with external factors, is crucial for LHON phenotype manifestation.
- Understanding variant-specific functional impacts aids in diagnosing and managing mitochondrial optic neuropathies.
