AI Article Synopsis
- - Dominant Optic Atrophy and Deafness (DOAD) can be linked to several related disorders, termed "DOA-plus," such as myopathy and peripheral neuropathy, and there's significant variability in symptoms among patients with the same genetic mutation in the OPA1 gene.
- - This study presents two families with the same OPA1 mutation (c.1334G>A), highlighting the differences in their clinical symptoms and biochemical characteristics despite having the same genetic change.
- - The researchers found varying levels of the mitochondrial molecule OMI/HTRA2 in the patients, suggesting that it could influence the variability in the symptoms of the "DOA-plus" phenotype, warranting further investigation into its role as a modifier gene.*
Article Abstract
Dominant Optic Atrophy and Deafness (DOAD) may be associated with one or more of the following disorders such as myopathy, progressive external ophthalmoplegia, peripheral neuropathy, and cerebellar atrophy ("DOA-plus"). Intra- and interfamilial variability of the "DOA-plus" phenotype is frequently observed in the majority of the patients carrying the same mutation in the OPA1 gene. We are describing two familial cases of "DOA-plus" carrying the same c.1334G>A (p.Arg445His) mutation in OPA1 and disclosing different clinical, pathological and biochemical features. The two patients showed different expression levels of the mitochondrial OMI/HTRA2 molecule, which acts as a mitochondrial stress sensor and has been described to interplay with OPA1 in in vitro studies. Our data offer the cue to inquire the role of OMI/HTRA2 as a modifier gene in determining the "DOAplus" phenotype variability.
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| http://dx.doi.org/10.1002/ajmg.a.61381 | DOI Listing |
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model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy.
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Autosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynamin GTPase () gene. encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus).
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Article Synopsis
- - Dominant Optic Atrophy and Deafness (DOAD) can be linked to several related disorders, termed "DOA-plus," such as myopathy and peripheral neuropathy, and there's significant variability in symptoms among patients with the same genetic mutation in the OPA1 gene.
- - This study presents two families with the same OPA1 mutation (c.1334G>A), highlighting the differences in their clinical symptoms and biochemical characteristics despite having the same genetic change.
- - The researchers found varying levels of the mitochondrial molecule OMI/HTRA2 in the patients, suggesting that it could influence the variability in the symptoms of the "DOA-plus" phenotype, warranting further investigation into its role as a modifier gene.*
OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database.
Orphanet J Rare Dis
September 2019
Unité Mixte de Recherche MITOVASC, CNRS 6015/INSERM 1083, Université d'Angers, Angers, France.
Background: The dysfunction of OPA1, a dynamin GTPase involved in mitochondrial fusion, is responsible for a large spectrum of neurological disorders, each of which includes optic neuropathy. The database dedicated to OPA1 ( https://www.lovd.
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