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

ABSTRACT: 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,

SUBMITTER: Vidali S 

PROVIDER: S-EPMC8649870 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature