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Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups

Leber Hereditary Optic Neuropathy (LHON) affects a minority of carriers of causative mitochondrial DNA mutations. We investigated a cohort of patients with LHON, including m.11778G>A, m.3460G>A, m.14484T>C and DNAJC30 c.152A>G variants, and their asymptomatic maternal carrier relatives f...

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Autores principales: Quigley, Clare, Stephenson, Kirk A. J., Kenna, Paul, Cassidy, Lorraine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864201/
https://www.ncbi.nlm.nih.gov/pubmed/36674591
http://dx.doi.org/10.3390/ijms24021068
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author Quigley, Clare
Stephenson, Kirk A. J.
Kenna, Paul
Cassidy, Lorraine
author_facet Quigley, Clare
Stephenson, Kirk A. J.
Kenna, Paul
Cassidy, Lorraine
author_sort Quigley, Clare
collection PubMed
description Leber Hereditary Optic Neuropathy (LHON) affects a minority of carriers of causative mitochondrial DNA mutations. We investigated a cohort of patients with LHON, including m.11778G>A, m.3460G>A, m.14484T>C and DNAJC30 c.152A>G variants, and their asymptomatic maternal carrier relatives for additional potential associations with vision loss. We assessed visual acuity, optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer (RNFL), visually evoked potential including P-100 latency, and full mitochondrial genome sequencing. Comparison was made with a reference standard for OCT; European Descent, Heidelberg Engineering ©; and electrophysiology measurements with in-house normative ranges. RNFL was thinned overall in LHON patients (n = 12); median global RNFL −54 μm in the right eye (RE) and −50 μm in the left eye (LE) versus normal, and was found to be normal overall in asymptomatic carriers at +1 μm RE and −2 μm LE (n = 16). In four asymptomatic carriers there was RNFL thinning found either unilaterally or bilaterally; these cases were associated with isolated delay in P-100 latency (25%), delay and reduced visual acuity (50%), or reduced visual acuity without P-100 latency delay (25%). Optic nerve dysfunction was associated with mitochondrial haplogroup H and HV, versus non-H haplogroups, in the asymptomatic carriers (Fisher’s exact test, p = 0.05). Our findings suggest that optic nerve abnormalities may be identified in asymptomatic LHON mitochondrial mutation carriers, which may be associated with optic nerve dysfunction. For asymptomatic carriers these findings were associated with mitochondrial haplogroup H and HV.
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spelling pubmed-98642012023-01-22 Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups Quigley, Clare Stephenson, Kirk A. J. Kenna, Paul Cassidy, Lorraine Int J Mol Sci Article Leber Hereditary Optic Neuropathy (LHON) affects a minority of carriers of causative mitochondrial DNA mutations. We investigated a cohort of patients with LHON, including m.11778G>A, m.3460G>A, m.14484T>C and DNAJC30 c.152A>G variants, and their asymptomatic maternal carrier relatives for additional potential associations with vision loss. We assessed visual acuity, optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer (RNFL), visually evoked potential including P-100 latency, and full mitochondrial genome sequencing. Comparison was made with a reference standard for OCT; European Descent, Heidelberg Engineering ©; and electrophysiology measurements with in-house normative ranges. RNFL was thinned overall in LHON patients (n = 12); median global RNFL −54 μm in the right eye (RE) and −50 μm in the left eye (LE) versus normal, and was found to be normal overall in asymptomatic carriers at +1 μm RE and −2 μm LE (n = 16). In four asymptomatic carriers there was RNFL thinning found either unilaterally or bilaterally; these cases were associated with isolated delay in P-100 latency (25%), delay and reduced visual acuity (50%), or reduced visual acuity without P-100 latency delay (25%). Optic nerve dysfunction was associated with mitochondrial haplogroup H and HV, versus non-H haplogroups, in the asymptomatic carriers (Fisher’s exact test, p = 0.05). Our findings suggest that optic nerve abnormalities may be identified in asymptomatic LHON mitochondrial mutation carriers, which may be associated with optic nerve dysfunction. For asymptomatic carriers these findings were associated with mitochondrial haplogroup H and HV. MDPI 2023-01-05 /pmc/articles/PMC9864201/ /pubmed/36674591 http://dx.doi.org/10.3390/ijms24021068 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Quigley, Clare
Stephenson, Kirk A. J.
Kenna, Paul
Cassidy, Lorraine
Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
title Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
title_full Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
title_fullStr Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
title_full_unstemmed Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
title_short Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
title_sort optic nerve structural and functional changes in lhon-affected and asymptomatic maternal relatives: association with h and hv mitochondrial haplogroups
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864201/
https://www.ncbi.nlm.nih.gov/pubmed/36674591
http://dx.doi.org/10.3390/ijms24021068
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