Identification and characterization of the novel point mutation m.3634A>G in the mitochondrial MT-ND1 gene associated with LHON syndrome

Lidia Carreño-Gago, Josep Gamez, Yolanda Cámara, Elena Alvarez de la Campa, Juan Sebastian Aller-Alvarez, Dulce Moncho, Maria Salvado, Alicia Galan, Xavier de la Cruz, Tomàs Pinós, Elena García-Arumí

    Research output: Contribution to journalArticleResearchpeer-review

    4 Citations (Scopus)

    Abstract

    © 2016 Elsevier B.V. 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.
    Original languageEnglish
    Pages (from-to)182-187
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1863
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2017

    Keywords

    • Cybrids
    • LHON syndrome
    • MT-ND1
    • mtDNA
    • Novel mutation

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