Case report: A rare variant m.4135T>C in the MT-ND1 gene leads to Leber hereditary optic neuropathy and altered respiratory chain supercomplexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F23%3A10466089" target="_blank" >RIV/00216208:11110/23:10466089 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/23:10466089 RIV/00064165:_____/23:10466089

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Qa8M1gMoju" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Qa8M1gMoju</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fgene.2023.1182288" target="_blank" >10.3389/fgene.2023.1182288</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Case report: A rare variant m.4135T>C in the MT-ND1 gene leads to Leber hereditary optic neuropathy and altered respiratory chain supercomplexes

Popis výsledku v původním jazyce

Leber hereditary optic neuropathy is a primary mitochondrial disease characterized by acute visual loss due to the degeneration of retinal ganglion cells. In this study, we describe a patient carrying a rare missense heteroplasmic variant in MT-ND1, NC_012920.1:m.4135T&gt;C (p.Tyr277His) manifesting with a typical bilateral painless decrease of the visual function, triggered by physical exercise or higher ambient temperature. Functional studies in muscle and fibroblasts show that amino acid substitution Tyr277 with His leads to only a negligibly decreased level of respiratory chain complex I (CI), but the formation of supercomplexes and the activity of the enzyme are disturbed noticeably. Our data indicate that although CI is successfully assembled in the patient&apos;s mitochondria, its function is hampered by the m.4135T&gt;C variant, probably by stabilizing CI in its inactive form. We conclude that the m.4135T&gt;C variant together with a combination of external factors is necessary to manifest the phenotype.

Název v anglickém jazyce

Case report: A rare variant m.4135T>C in the MT-ND1 gene leads to Leber hereditary optic neuropathy and altered respiratory chain supercomplexes

Popis výsledku anglicky

Leber hereditary optic neuropathy is a primary mitochondrial disease characterized by acute visual loss due to the degeneration of retinal ganglion cells. In this study, we describe a patient carrying a rare missense heteroplasmic variant in MT-ND1, NC_012920.1:m.4135T&gt;C (p.Tyr277His) manifesting with a typical bilateral painless decrease of the visual function, triggered by physical exercise or higher ambient temperature. Functional studies in muscle and fibroblasts show that amino acid substitution Tyr277 with His leads to only a negligibly decreased level of respiratory chain complex I (CI), but the formation of supercomplexes and the activity of the enzyme are disturbed noticeably. Our data indicate that although CI is successfully assembled in the patient&apos;s mitochondria, its function is hampered by the m.4135T&gt;C variant, probably by stabilizing CI in its inactive form. We conclude that the m.4135T&gt;C variant together with a combination of external factors is necessary to manifest the phenotype.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

<a href="/cs/project/NU22-07-00614" target="_blank" >NU22-07-00614: Mitochondriální optické neuropatie: komplexní genetická a metabolomická analýza k určení vzácných příčin onemocnění a hledání nových biomarkerů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Genetics

ISSN

1664-8021

e-ISSN

1664-8021

Svazek periodika

14

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

1182288

Kód UT WoS článku

001016692600001

EID výsledku v databázi Scopus

2-s2.0-85161001836