Journalartikel
Autorenliste: Gangfuss, Andrea; Rating, Philipp; Ferreira, Tomas; Hentschel, Andreas; Della Marina, Adela; Koelbel, Heike; Sickmann, Albert; Abicht, Angela; Kraft, Florian; Ruck, Tobias; Boehm, Johann; Schaenzer, Anne; Schara-Schmidt, Ulrike; Neuhann, Teresa M.; Horvath, Rita; Roos, Andreas
Jahr der Veröffentlichung: 2024
Seiten: 485-491
Zeitschrift: Journal of Neuromuscular Diseases
Bandnummer: 11
Heftnummer: 2
ISSN: 2214-3599
eISSN: 2214-3602
Open Access Status: Hybrid
DOI Link: https://doi.org/10.3233/JND-230181
Verlag: SAGE Publications
Background: The NADH dehydrogenase [ubiquinone] iron-sulfur protein 6 (NDUFS6) gene encodes for an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Bi-allelic NDUFS6 variants have been linked with a severe disorder mostly reported as a lethal infantile mitochondrial disease (LMID) or Leigh syndrome (LS). Objective: Here, we identified a homozygous variant (c.309 + 5 G > A) in NDUFS6 in one male patient with axonal neuropathy accompanied by loss of small fibers in skin biopsy and further complicated by optic atrophy and borderline intellectual disability. Methods: To address the pathogenicity of the variant, biochemical studies (mtDNA copy number quantification, ELISA, Proteomic profiling) of patient-derived leukocytes were performed. Results: The analyses revealed loss of NDUFS6 protein associated with a decrease of three further mitochondrial NADH dehydrogenase subunit/assembly proteins (NDUFA12, NDUFS4 and NDUFV1). Mitochondrial copy number is not altered in leukocytes and the mitochondrial biomarker GDF15 is not significantly changed in serum. Conclusions: Hence, our combined clinical and biochemical data strengthen the concept of NDUFS6 being causative for a very rare form of axonal neuropathy associated with optic atrophy and borderline intellectual disability, and thus expand (i) the molecular genetic landscape of neuropathies and (ii) the clinical spectrum of NDUFS6-associated phenotypes.
Abstract:
Zitierstile
Harvard-Zitierstil: Gangfuss, A., Rating, P., Ferreira, T., Hentschel, A., Della Marina, A., Koelbel, H., et al. (2024) A Homozygous NDUFS6 Variant Associated with Neuropathy and Optic Atrophy, Journal of Neuromuscular Diseases, 11(2), pp. 485-491. https://doi.org/10.3233/JND-230181
APA-Zitierstil: Gangfuss, A., Rating, P., Ferreira, T., Hentschel, A., Della Marina, A., Koelbel, H., Sickmann, A., Abicht, A., Kraft, F., Ruck, T., Boehm, J., Schaenzer, A., Schara-Schmidt, U., Neuhann, T., Horvath, R., & Roos, A. (2024). A Homozygous NDUFS6 Variant Associated with Neuropathy and Optic Atrophy. Journal of Neuromuscular Diseases. 11(2), 485-491. https://doi.org/10.3233/JND-230181
Schlagwörter
axonal neuropathy; Charcot-Marie-Tooth disease; COMPLEX I DEFICIENCY; NDUFS6; white blood cell proteomics
