case_images: PMC8027302_01
case_images: Automated Humphrey visual field of patient described in Case 1 performed 3 weeks from symptomatic decline of vision in the second eye, i.e., the right eye. A temporal defect is noted in the RE and a central defect in the LE.
case_images: fneur-12-652590-g0001.jpg
case_images: PMC8027302_01_fneur-12-652590-g0001.jpg
case_images: F1
case_images: On examination, BCVA was 0.13 in the RE and hand motion in the LE Humphrey  automated visual fields 24-2 (Carl Zeiss Meditec.Inc , Jena) showed a temporal defect encroaching fixation in the RE and a large central scotoma in the LE (Figure 1).
case_images: PMC8027302_02
case_images: Graphic of respiratory chain enzyme activities in the muscle biopsy of the two patients described in Case 1 and Case 2, as compared to normal controls. There is a mild reduction in complex I + III.
case_images: fneur-12-652590-g0002.jpg
case_images: PMC8027302_02_fneur-12-652590-g0002.jpg
case_images: F2
case_images: Measurements of the respiratory chain enzyme activities revealed a mild reduction in complex I+III in both the patient and her son while all other activities (including complex I) were found to be within the reference range (Figure 2).
case_images: (A) Sanger sequencing of DNA from skeletal muscle from case 1 showing homoplasmic m.13345G>A mutation. (B) MtSNP Database mtSAP alignment of 11 mammals showing that the residue Ala337 and the adjacent aminoacids are very well-conserved (all 61 mammals in the database have alanine at this position). (C) A human cryo-EM structure of complex I (PDB:5XTD), with ND5 highlighted in blue. Frontal (right) and lateral (left) view. Ala337 is buried inside the protein structure and its position is indicated with black/white circles. (D) Pathogenicity prediction score of different tools. PROVEAN, Rhapsody, PolyPhen-2, EVmutation and SIFT. (E) A337 is shown in the above structure with PyMOL version 2.3.4. (Schrodinger, LLC.) with its closest interactors Leu457 and Val96. Dotted lines mark the quantified distances between the side chain atoms. The color codes for hydrophobicity, whereby red is strongly hydrophobic and white is strongly hydrophilic. This indicates that Ala337 is in a strongly hydrophobic environment. The plugin color_h was used on the basis of a previously established hydrophobicity grading.
case_images: fneur-12-652590-g0003.jpg
case_images: PMC8027302_02_fneur-12-652590-g0003.jpg
case_images: F3
case_images: NADH:ubiquinone oxidoreductase core subunit 5 (MT-ND5) in homoplasmy and was assumed to be related to the optic neuropathy (Figure 3A). No other disease-causing mutations that could explain the phenotype were identified.
case_images: Fundus-photography of patient described in Case 1 taken 5 months from presentation to the ophthalmic clinic. There is bilateral pallor of the optic disk and a non-related epiretinal membrane in the left eye 5 months after presentation.
case_images: fneur-12-652590-g0004.jpg
case_images: PMC8027302_02_fneur-12-652590-g0004.jpg
case_images: F4
case_images: During the months following onset, optic atrophy developed (Figure 4).