A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy

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http://hdl.handle.net/10138/237062

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Jackson , C B , Hahn , D , Schroter , B , Richter , U , Battersby , B J , Schmitt-Mechelke , T , Marttinen , P , Nuoffer , J-M & Schaller , A 2017 , ' A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy ' , European Journal of Medical Genetics , vol. 60 , no. 6 , pp. 345-351 . https://doi.org/10.1016/j.ejmg.2017.04.006

Title: A novel mitochondrial ATP6 frameshift mutation causing isolated complex V deficiency, ataxia and encephalomyopathy
Author: Jackson, Christopher B.; Hahn, Dagmar; Schroter, Barbara; Richter, Uwe; Battersby, Brendan J.; Schmitt-Mechelke, Thomas; Marttinen, Paula; Nuoffer, Jean-Marc; Schaller, Andre
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2017-06
Language: eng
Number of pages: 7
Belongs to series: European Journal of Medical Genetics
ISSN: 1769-7212
URI: http://hdl.handle.net/10138/237062
Abstract: We describe a novel frameshift mutation in the mitochondrial ATP6 gene in a 4-year-old girl associated with ataxia, microcephaly, developmental delay and intellectual disability. A heteroplasmic frameshift mutation in the MT-ATP6 gene was confirmed in the patient's skeletal muscle and blood. The mutation was not detectable in the mother's DNA extracted from blood or buccal cells. Enzymatic and oxymetric analysis of the mitochondrial respiratory system in the patients' skeletal muscle and skin fibroblasts demonstrated an isolated complex V deficiency. Native PAGE with subsequent immunoblotting for complex V revealed impaired complex V assembly and accumulation of ATPase subcomplexes. Whilst northern blotting confirmed equal presence of ATP8/6 mRNA, metabolic S-35-labelling of mitochondrial translation products showed a severe depletion of the ATP6 protein together with aberrant translation product accumulation. In conclusion, this novel isolated complex V defect expands the clinical and genetic spectrum of mitochondrial defects of complex V deficiency. Furthermore, this work confirms the benefit of native PAGE as an additional diagnostic method for the identification of OXPHOS defects, as the presence of complex V subcomplexes is associated with pathogenic mutations of mtDNA. (C) 2017 Elsevier Masson SAS. All rights reserved.
Subject: MT-ATP6
ATP synthase
Mitochondrial disease
Mitochondrial DNA (mtDNA)
Complex V deficiency
BIOCHEMICAL-CHARACTERIZATION
HYPERTROPHIC CARDIOMYOPATHY
POINT MUTATION
LEIGH-SYNDROME
GENE MUTATION
SYNTHASE
DNA
ORGANIZATION
DISORDERS
DISEASES
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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