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Characterising a homozygous two-exon deletion in UQCRH: comparing human and mouse phenotypes

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00559909" target="_blank" >RIV/68378050:_____/21:00559909 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.embopress.org/doi/full/10.15252/emmm.202114397" target="_blank" >https://www.embopress.org/doi/full/10.15252/emmm.202114397</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.15252/emmm.202114397" target="_blank" >10.15252/emmm.202114397</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Characterising a homozygous two-exon deletion in UQCRH: comparing human and mouse phenotypes

  • Original language description

    Mitochondrial disorders are clinically and genetically diverse, with isolated complex III (CIII) deficiency being relatively rare. Here, we describe two affected cousins, presenting with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy. Genetic investigations in both cases identified a homozygous deletion of exons 2 and 3 of UQCRH, which encodes a structural complex III (CIII) subunit. We generated a mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh(-/-)), which also presented with lactic acidosis and hyperammonaemia, but had a more severe, non-episodic phenotype, resulting in failure to thrive and early death. The biochemical phenotypes observed in patient and Uqcrh(-/-) mouse tissues were remarkably similar, displaying impaired CIII activity, decreased molecular weight of fully assembled holoenzyme and an increase of an unexpected large supercomplex (S-XL), comprising mostly of one complex I (CI) dimer and one CIII dimer. This phenotypic similarity along with lentiviral rescue experiments in patient fibroblasts verifies the pathogenicity of the shared genetic defect, demonstrating that the Uqcrh(-/-) mouse is a valuable model for future studies of human CIII deficiency.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30102 - Immunology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2021

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    EMBO Molecular Medicine

  • ISSN

    1757-4676

  • e-ISSN

    1757-4684

  • Volume of the periodical

    13

  • Issue of the periodical within the volume

    12

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    19

  • Pages from-to

    e14397

  • UT code for WoS article

    000715894100001

  • EID of the result in the Scopus database