@article{18987,
  abstract     = {Biallelic variants in NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen (H))-ubiquinone oxidoreductase 1 alpha subcomplex 13 have been linked to mitochondrial complex I deficiency, nuclear type 28, based on three affected individuals from two families. With only two families reported, the clinical and molecular spectrum of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13–related diseases remains unclear. We report 10 additional affected individuals from nine independent families, identifying four missense variants (including recurrent c.170G > A) and three ultra-rare or novel predicted loss-of-function biallelic variants. Updated clinical–radiological data from previously reported families and a literature review compiling clinical features of all reported patients with isolated complex I deficiency caused by 43 genes encoding complex I subunits and assembly factors are also provided. Our cohort (mean age 7.8 ± 5.4 years; range 2.5–18) predominantly presented a moderate-to-severe neurodevelopmental syndrome with oculomotor abnormalities (84%), spasticity/hypertonia (83%), hypotonia (69%), cerebellar ataxia (66%), movement disorders (58%) and epilepsy (46%). Neuroimaging revealed bilateral symmetric T2 hyperintense substantia nigra lesions (91.6%) and optic nerve atrophy (66.6%). Protein modeling suggests missense variants destabilize a critical junction between the hydrophilic and membrane arms of complex I. Fibroblasts from two patients showed reduced complex I activity and compensatory complex IV activity increase. This study characterizes NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13–related disease in 13 individuals, highlighting genotype–phenotype correlations.},
  author       = {Kaiyrzhanov, Rauan and Thompson, Kyle and Efthymiou, Stephanie and Mukushev, Askhat and Zharylkassyn, Akbota and Prasad, Chitra and Karimiani, Ehsan Ghayoor and Alvi, Javeria Raza and Niyazov, Dmitriy and Alahmad, Ahmad and Babaei, Meisam and Tajsharghi, Homa and Albash, Buthaina and Alaqeel, Ahmad and Charif, Majida and Hashemi, Narges and Heidari, Morteza and Kalantar, Seyed Mehdi and Lenaers, Guy and Mehrjardi, Mohammad Yahya Vahidi and Srinivasan, Varunvenkat M. and Gowda, Vykuntaraju K. and Mirabutalebi, Seyed Hamidreza and Carere, Deanna Alexis and Movahedinia, Mojtaba and Murphy, David and Mcfarland, Robert and Abdel-Hamid, Mohamed S. and Elhossini, Rasha M. and Alavi, Shahryar and Napier, Melanie and Belanger-Quintana, Amaya and Prasad, Asuri N. and Jakobczyk, Jessica and Roubertie, Agathe and Rupar, Tony and Sultan, Tipu and Toosi, Mehran Beiraghi and Sazanov, Leonid A and Severino, Mariasavina and Houlden, Henry and Taylor, Robert W. and Maroofian, Reza},
  issn         = {2632-1297},
  journal      = {Brain Communications},
  number       = {1},
  publisher    = {Oxford University Press},
  title        = {{Biallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment}},
  doi          = {10.1093/braincomms/fcae453},
  volume       = {7},
  year         = {2025},
}