Long-term screening for primary mitochondrial DNA variants associated with Leber hereditary optic neuropathy: incidence, penetrance and clinical features.


Journal

Mitochondrion
ISSN: 1872-8278
Titre abrégé: Mitochondrion
Pays: Netherlands
ID NLM: 100968751

Informations de publication

Date de publication:
09 2020
Historique:
received: 18 12 2019
revised: 22 06 2020
accepted: 24 08 2020
pubmed: 31 8 2020
medline: 30 3 2021
entrez: 31 8 2020
Statut: ppublish

Résumé

Leber hereditary optic neuropathy (LHON) is a neurodegenerative disorder characterised by bilateral, painless, subacute, central vision loss caused by pathogenic sequence variants in mitochondrial DNA (mtDNA). Over the course of 20 years, 734 people were systematically screened by our diagnostic laboratory for suspected LHON or for being at risk of LHON, with 98 found to harbour one of the three primary pathogenic mtDNA variants. Detection incidences were: 0.95% for NC_012920.1(MT-ND1):m.3460G>A; 9.4% for (MT-ND4):m.11778G>A; and 2.9% for (MT-ND6):m.14484T>C. The median age for symptomatic males was 27.3 years and for females 29.5 years, with a male to female ratio of 4.4:1 (62 males; 14 females). Most pathogenic variant carriers were propositi with the other individuals belonging to one of 14 pedigrees with noteworthy intra-family variability of clinical severity of the disease.

Identifiants

pubmed: 32861874
pii: S1567-7249(20)30176-8
doi: 10.1016/j.mito.2020.08.007
pii:
doi:

Substances chimiques

DNA, Mitochondrial 0
NADH dehydrogenase subunit 4 0
MT-ND6 protein, human EC 1.6.99.3
NADH Dehydrogenase EC 1.6.99.3
MT-ND1 protein, human EC 7.1.1.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

128-132

Informations de copyright

Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Auteurs

Rosetta Marotta (R)

St Vincent's Hospital Melbourne Mitochondrial and Autoimmune Neurological Disorders Laboratory, Department of Clinical Neurosciences and Neurological Research, 5th Floor Daly Wing, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. Electronic address: rosetta.marotta@svha.org.au.

Judy Chin (J)

St Vincent's Hospital Melbourne Mitochondrial and Autoimmune Neurological Disorders Laboratory, Department of Clinical Neurosciences and Neurological Research, 5th Floor Daly Wing, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

Maria Chiotis (M)

St Vincent's Hospital Melbourne Mitochondrial and Autoimmune Neurological Disorders Laboratory, Department of Clinical Neurosciences and Neurological Research, 5th Floor Daly Wing, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

Neil Shuey (N)

St Vincent's Hospital Melbourne Mitochondrial and Autoimmune Neurological Disorders Laboratory, Department of Clinical Neurosciences and Neurological Research, 5th Floor Daly Wing, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; Neuro-Ophthalmology Clinic at the Royal Victorian Eye and Ear Hospital, East Melbourne Victoria, Australia.

Steven J Collins (SJ)

St Vincent's Hospital Melbourne Mitochondrial and Autoimmune Neurological Disorders Laboratory, Department of Clinical Neurosciences and Neurological Research, 5th Floor Daly Wing, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

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Classifications MeSH