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Novel POLG splice site mutation and optic atrophy.
Margherita Milone1, Jing Wang, Teerin Liewluck
1Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. Milone.Margherita@mayo.edu
Archives of Neurology
|June 15, 2011
Summary
Novel POLG gene variants cause multisystem mitochondrial disorders with optic atrophy, mimicking OPA1-related conditions. This finding impacts genetic counseling for patients with early-onset vision loss and neurological symptoms.
Area of Science:
- Genetics
- Neurology
- Mitochondrial Biology
Background:
- Mitochondrial disorders are a group of debilitating genetic conditions affecting multiple organ systems.
- Optic atrophy, a key feature, can be associated with various genetic etiologies, including OPA1-related disorders.
Observation:
- Two unrelated patients presented with multisystem mitochondrial disorders; one had optic atrophy, dyschromatopsia, and progressive external ophthalmoplegia, while the other experienced hearing loss and parkinsonism.
- Muscle biopsies revealed characteristic ragged-red, ragged-blue, and cytochrome c oxidase-negative fibers, indicative of mitochondrial dysfunction.
Findings:
- Genetic analysis excluded OPA1 mutations but identified multiple mitochondrial DNA deletions.
- Sequencing of the POLG gene revealed a novel variant (c.3104 + 3A>T) in both patients, leading to exon 18 skipping.
- Patient 1 was compound heterozygous for POLG p.F749S, and Patient 2 for p.G848S, confirming POLG as the causative gene.
Implications:
- Early-onset dyschromatopsia and optic atrophy can be manifestations of POLG-related disorders, not exclusively OPA1-related conditions.
- Accurate molecular diagnosis of POLG mutations is crucial for precise genetic counseling and understanding disease progression.
- This study expands the phenotypic spectrum of POLG-related mitochondrial disorders.
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