Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation.

Abstract

PURPOSE:

This study was designed to assess the effect of mitochondrial DNA (mtDNA) mutation T8993C on cone structure in a family expressing neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome.

METHODS:

Five family members were studied, using clinical examination, nerve conduction studies, perimetry, optical coherence tomography (OCT) measures of central retinal thickness, and electroretinography. High-resolution images of cone structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) were obtained in four subjects with stable fixation. Cone spacing was compared to 18 age-similar normal subjects and converted to z-scores at each location where unambiguous cones were identified. Tissue levels of T8993C mutant heteroplasmy in blood and hair follicles were quantified using real-time allele-refractory mutations system (ARMS) quantitative polymerase chain reaction (qPCR).

RESULTS:

Subjects expressing the T8993C mutation showed varying levels of disease severity. The subject with the lowest mutant load (42%-54%) showed no neurologic or retinal abnormalities. The remaining four subjects with over 77% mutant load all expressed severe neurologic and/or retinal abnormalities. AOSLO images revealed three patterns of cone spacing: pattern 1, normal; pattern 2, increased cone spacing within a contiguous cone mosaic; and pattern 3, patchy cone loss with increased cone spacing. Visual function was most severely affected in pattern 3.

CONCLUSIONS:

High levels of T8993C mutant load were associated with severe neurologic or visual dysfunction, while lower levels caused no detectable abnormalities. Visual function was better in patients with a contiguous and regular cone mosaic. Patients expressing high levels of the mtDNA T8993C mutation show abnormal cone structure, suggesting normal mitochondrial DNA is necessary for normal waveguiding by cones.

• Authors: Michael K Yoon, Austin Roorda, Yuhua Zhang, Chiaki Nakanishi, Lee-Jun C Wong, Qing Zhang, Leslie Gillum, Ari Green, Jacque L Duncan
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 50 Issue 4 Pg. 1838-47 (Apr 2009) ISSN: 1552-5783 [Electronic] United States
• PMID: 18997096 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA, Mitochondrial

Topics

• Adolescent
• Adult
• Age of Onset
• Ataxia (genetics, pathology)
• DNA Mutational Analysis
• DNA, Mitochondrial (genetics)
• Female
• Humans
• Lasers
• Male
• Middle Aged
• Muscle Weakness (genetics, pathology)
• Ophthalmoscopy
• Pedigree
• Point Mutation
• Polymerase Chain Reaction
• Retinal Cone Photoreceptor Cells (pathology)
• Retinitis Pigmentosa (genetics, pathology)
• Syndrome
• Tomography, Optical Coherence