Identification and characterization of the novel point mutation m.3634A>G in the mitochondrial MT-ND1 gene associated with LHON syndrome.
Biochim Biophys Acta Mol Basis Dis
; 1863(1): 182-187, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27613247
ABSTRACT
Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease characterized by bilateral acute or subacute progressive central visual loss. Most cases of LHON syndrome are caused by point mutations in the MT-ND1, MT-ND4, and MT-ND6 genes. Here, we report a novel homoplasmic mutation in the MT-ND1 gene (m.3634A>G, p.Ser110Gly) in a patient with the classical clinical features of LHON syndrome. Several observations support the idea that the mutation is pathogenic and involved in the clinical phenotype of the patient 1) The mutation affected a highly conserved amino acid, 2) A pathogenic mutation in the same amino acid (m.3635G>A, p.Ser110Asn) was previously reported in a patient with LHON syndrome, 3) The mutation is not recorded in the Mitomap or Human Mitochondrial Genome Database, 4) In silico predictors classified the mutation as "probably damaging", and 5) Cybrids carrying the mutation showed decreased Complex I enzyme activity, lower cell proliferation, and decreased mitochondrial membrane potential relative to control cybrids.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutação Puntual
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Atrofia Óptica Hereditária de Leber
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NADH Desidrogenase
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article