BI-ALLELIC PATHOGENIC VARIANTS IN NDUFC2 CAUSE EARLY-ONSET LEIGH SYNDROME AND STALLED BIOGENESIS OF COMPLEX I

ABSTRACT: Leigh syndrome is a progressive neurodegenerative disorder, most commonly observed in paediatric mitochondrial disease and is often associated with pathogenic variants in complex I structural subunits or assembly factors resulting in isolated respiratory chain complex I deficiency. Clinical heterogeneity has been reported, but key diagnostic findings are developmental regression, elevated lactate and characteristic neuroimaging abnormalities. Here, we describe three affected children from two unrelated families who presented with Leigh syndrome due to homozygous variants (c.346_*7del and c.173A>T p.His58Leu) in NDUFC2, encoding a complex I subunit. Biochemical and functional investigation of subjects' fibroblasts confirmed a severe defect in complex I activity, subunit expression and as

SUBMITTER: Prof. Robert, W. Taylor 

PROVIDER: S-SCDT-EMM-2020-12619 | biostudies-other |

REPOSITORIES: biostudies-other