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NDUFB8 mutations cause mitochondrial complex I deficiency in individuals with leigh-like encephalomyopathy.
Am. J. Hum. Genet. 102, 460-467 (2018)
DOI PMC
Verlagsversion online verfügbar vsl. 11/2018 
Respiratory chain complex I deficiency is the most frequently identified biochemical defect in childhood mitochondrial diseases. Clinical symptoms range from fatal infantile lactic acidosis to Leigh syndrome and other encephalomyopathies or cardiomyopathies. To date, disease-causing variants in genes coding for 27 complex I subunits, including 7 mitochondrial DNA genes, and in 11 genes encoding complex I assembly factors have been reported. Here, we describe rare biallelic variants in NDUFB8 encoding a complex I accessory subunit revealed by whole-exome sequencing in two individuals from two families. Both presented with a progressive course of disease with encephalo(cardio) myopathic features including muscular hypotonia, cardiac hypertrophy, respiratory failure, failure to thrive, and developmental delay. Blood lactate was elevated. Neuroimaging disclosed progressive changes in the basal ganglia and either brain stem or internal capsule. Biochemical analyses showed an isolated decrease in complex I enzymatic activity in muscle and fibroblasts. Complementation studies by expression of wild-type NDUFB8 in cells from affected individuals restored mitochondrial function, confirming NDUFB8 variants as the cause of complex I deficiency. Hereby we establish NDUFB8 as a relevant gene in childhood-onset mitochondrial disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Complex I ; Lactic Acidosis ; Leigh Syndrome ; Mitochondria ; Nadh Dehydrogenase ; Oxidative Phosphorylation ; Respiratory Chain; Respiratory-chain Deficiency; Acad9 Mutations; Disease; Architecture; Diagnosis; Features
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Quellenangaben Band: 102, Heft: 3, Seiten: 460-467 Artikelnummer: , Supplement: ,
Verlag Elsevier ; Cell Press
Verlagsort New York, NY
Begutachtungsstatus peer-reviewed