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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene
European Journal of Human Genetics, Volume 22, No. 2, Year 2014
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Description
Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are severe autosomal recessive disorders associated with decreased mtDNA copy number in clinically affected tissues. The hepatocerebral form (mtDNA depletion in liver and brain) has been associated with mutations in the POLG, PEO1 (Twinkle), DGUOK and MPV17 genes, the latter encoding a mitochondrial inner membrane protein of unknown function. The aims of this study were to clarify further the clinical, biochemical, cellular and molecular genetic features associated with MDS due to MPV17 gene mutations. We identified 12 pathogenic mutations in the MPV17 gene, of which 11 are novel, in 17 patients from 12 families. All patients manifested liver disease. Poor feeding, hypoglycaemia, raised serum lactate, hypotonia and faltering growth were common presenting features. mtDNA depletion in liver was demonstrated in all seven cases where liver tissue was available. Mosaic mtDNA depletion was found in primary fibroblasts by PicoGreen staining. These results confirm that MPV17 mutations are an important cause of hepatocerebral mtDNA depletion syndrome, and provide the first demonstration of mosaic mtDNA depletion in human MPV17 mutant fibroblast cultures. We found that a severe clinical phenotype was associated with profound tissue-specific mtDNA depletion in liver, and, in some cases, mosaic mtDNA depletion in fibroblasts. © 2014 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Uusimaa, Johanna
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Finland, Oulu
Oulun Yliopisto
Evans, Julie C.
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Smith, Conrad
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Butterworth, Anna
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
Craig, Kate
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
Ashley, Neil
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Liao, Chunyan
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Carver, Janet
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Diot, Alan
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Macleod, Lorna
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Hargreaves, Iain Parry
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Al-Hussaini, Abdulrahman Abdullah
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Faqeih, Eissa Ali
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Asery, Ali Talee
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Al-Balwi, Mohammed Ali
Unknown Affiliation
Eyaid, Wafaa M.
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Al-Sunaid, Areej
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Kelly, Deirdre Anne K.
United Kingdom, Birmingham
Birmingham Children's Hospital
van Mourik, Indra D.M.
United Kingdom, Birmingham
Birmingham Children's Hospital
Ball, Sarah
United Kingdom, Birmingham
Birmingham Children's Hospital
Jarvis, Joanna
United Kingdom, Birmingham
Birmingham Women's Hospital
Mulay, Arundhati
United Kingdom, Walsall
Walsall Manor Hospital
Hadzic, Nedim
United Kingdom, London
King's College Hospital
Samyn, Marianne
United Kingdom, London
King's College Hospital
Baker, A. J.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Rahman, Shamima
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Stewart, Helen
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Morris, Andrew A.M.
United Kingdom, London
St Mary's Hospital
Seller, Anneke
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Fratter, Carl
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Taylor, Robert William
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
Poulton, Joanna J.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Statistics
Citations: 65
Authors: 32
Affiliations: 13
Identifiers
Doi:
10.1038/ejhg.2013.112
ISSN:
10184813
e-ISSN:
14765438
Research Areas
Genetics And Genomics