Bi-allelic variants in NDUFA5 cause a mitochondriopathy with complex I deficiency

We identify bi-allelic NDUFA5 variants in four individuals from three families with mitochondrial complex I deficiency. Genomic, transcriptomic, proteomic, and biochemical studies across patient tissues, complemented by a zebrafish model, characterize a variable multisystem disease with cardiac, hematological, and Leigh syndrome-like neurological features, expanding the spectrum of complex I mitochondriopathies.