A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia

• Published in: Clinical genetics Vol. 91; no. 3; pp. 441 - 447
• Main Authors: Torraco, A., Bianchi, M., Verrigni, D., Gelmetti, V., Riley, L., Niceta, M., Martinelli, D., Montanari, A., Guo, Y., Rizza, T., Diodato, D., Di Nottia, M., Lucarelli, B., Sorrentino, F., Piemonte, F., Francisci, S., Tartaglia, M., Valente, E.M., Dionisi‐Vici, C., Christodoulou, J., Bertini, E., Carrozzo, R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2017
• Subjects: Acidosis; Acidosis, Lactic - complications; Acidosis, Lactic - genetics; Acidosis, Lactic - physiopathology; Anemia; Anemia, Sideroblastic - complications; Anemia, Sideroblastic - genetics; Anemia, Sideroblastic - physiopathology; Cardiomyopathy; Child; DNA, Mitochondrial - genetics; Electron transport chain; Electron Transport Complex I - deficiency; Electron Transport Complex I - genetics; Genetic Predisposition to Disease; Genotype & phenotype; Humans; Lactic acidosis; Male; Membrane proteins; Microphthalmia; Microphthalmos - genetics; Microphthalmos - physiopathology; Mitochondria; mitochondrial disease; Mutation; NADH-ubiquinone oxidoreductase; NDUFB11; OXPHOS; Pedigree; Phenotype; Phenotypes; Sideroblastic anemia; Supernumerary; Tyrosine-tRNA Ligase; OXPHOS; NDUFB11; mitochondrial disease; sideroblastic anemia
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12790

NDUFB11, a component of mitochondrial complex I, is a relatively small integral membrane protein, belonging to the “supernumerary” group of subunits, but proved to be absolutely essential for the assembly of an active complex I. Mutations in the X‐linked nuclear‐encoded NDUFB11 gene have recently been discovered in association with two distinct phenotypes, i.e. microphthalmia with linear skin defects and histiocytoid cardiomyopathy. We report on a male with complex I deficiency, caused by a de novo mutation in NDUFB11 and displaying early‐onset sideroblastic anemia as the unique feature. This is the third report that describes a mutation in NDUFB11, but all are associated with a different phenotype. Our results further expand the molecular spectrum and associated clinical phenotype of NDUFB11 defects.
Inactivation of CI due to a de novo mutation in NDUFB11 gene, encoding for a small and hydrophobic subunit of CI, produces a peculiar phenotype in our patient characterized by lactic acidosis and sideroblastic anemia