{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNDUFAF8 is an essential protein that functions as an assembly factor for mitochondrial complex I by interacting with the well‐characterized assembly factor NDUFAF5, thereby facilitating early steps in the formation of this critical respiratory complex. Biallelic pathogenic variants in NDUFAF8, including a recurrent deep-intronic splicing variant, have been identified in pediatric subjects with Leigh syndrome—a neurodegenerative disorder characterized by symmetrical brain lesions, motor impairment, and delayed development. Patient fibroblasts harboring these mutations exhibit a marked complex I deficiency, with complexome profiling revealing stalled assembly intermediates that reinforce the role of NDUFAF8 in early complex I assembly. Importantly, lentiviral transduction with wild-type NDUFAF8 cDNA was shown to ameliorate both the assembly defect and the biochemical deficiency, underscoring the protein’s critical function in mitochondrial bioenergetics and expanding the genetic heterogeneity associated with Leigh syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Charlotte L Alston, Mike T Veling, Juliana Heidler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2019.12.001"}], "href": "https://doi.org/10.1016/j.ajhg.2019.12.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31866046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31866046"}]}]}]}