A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia.
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.
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Torraco
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Bianchi
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Verrigni
Neurogenetics Unit, CSS-Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
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Gelmetti
Genetic Metabolic Disorders Research Unit, Children's Hospital at Westmead, Sydney, Australia.|Discipline of Paediatrics & Child Health, University of Sydney, Sydney, Australia.
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Riley
Division of Genetic Disorders and Rare Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Niceta
Division of Metabolism, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Martinelli
Pasteur Institute - Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.
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Montanari
Genetic Metabolic Disorders Research Unit, Children's Hospital at Westmead, Sydney, Australia.
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Guo
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Rizza
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Diodato
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Di Nottia
Stem Cell Transplant Unit, Department of Hematology and Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Lucarelli
UO Talassemici -Anemie Rare del Globulo Rosso, Ospedale S Eugenio, Rome, Italy.
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Sorrentino
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Piemonte
Department of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, Rome, Italy.
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Francisci
Division of Genetic Disorders and Rare Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Tartaglia
Section of Neurosciences, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
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Valente
Division of Metabolism, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Dionisi-Vici
Genetic Metabolic Disorders Research Unit, Children's Hospital at Westmead, Sydney, Australia.|Discipline of Paediatrics & Child Health, University of Sydney, Sydney, Australia.|Discipline of Genetic Medicine, University of Sydney, Sydney, Australia.
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Christodoulou
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Bertini
Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Carrozzo
D000140:Acidosis, Lactic / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D000756:Anemia, Sideroblastic / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008850:Microphthalmos / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014448:Tyrosine-tRNA Ligase
D004272:DNA, Mitochondrial; C518653:NDUFB11 protein, human; D014448:Tyrosine-tRNA Ligase; D042967:Electron Transport Complex I
NDUFB11; OXPHOS; mitochondrial disease; sideroblastic anemia