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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-03-2018 | Genetics

Mitochondrial A3243G mutation results in corneal endothelial polymegathism

Authors: Mathieu F. Bakhoum, Wei-Pu Wu, Eugenia C. White, Jesse D. Sengillo, Christian Sanfilippo, Marcelle M. Morcos, K. Bailey Freund, Henry D. Perry, David Sarraf, Stephen H. Tsang

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 3/2018

Abstract

Purpose

The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities.

Methods

We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing.

Results

Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm², the average endothelial cell size was 442 ± 103 μm² and the average central corneal thickness (CCT) was 551 ± 33 μm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients’ age. None of the patients had signs of corneal edema. One patient had a pre-Descemet’s opacity.

Conclusions

In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.

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Title: Mitochondrial A3243G mutation results in corneal endothelial polymegathism
Authors: Mathieu F. Bakhoum
Wei-Pu Wu
Eugenia C. White
Jesse D. Sengillo
Christian Sanfilippo
Marcelle M. Morcos
K. Bailey Freund
Henry D. Perry
David Sarraf
Stephen H. Tsang
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 3/2018
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-018-3914-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mitochondrial A3243G mutation results in corneal endothelial polymegathism

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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