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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Clinical and molecular characteristics of mitochondrial DNA depletion syndrome associated with neonatal cholestasis and liver failure
Journal of Pediatrics, Volume 164, No. 3, Year 2014
Notification
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Description
Objective To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants with cholestasis and liver failure and to further clarify the clinical, biochemical, radiologic, histopathologic, and molecular features associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene mutations. Study design We studied 20 infants with suspected hepatocerebral MDS referred to our tertiary care center between 2007 and 2013. Genomic DNA was isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard methods. Mitochondrial DNA copy number relative to nuclear DNA levels was determined in muscle and/or liver DNA using real-time quantitative polymerase chain reaction and compared with age-matched controls. Nuclear candidate genes, including polymerase γ, MPV17, and DGUOK were sequenced using standard analyses. Results We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period. All of the 11 patients manifested cholestasis that was followed by a rapidly progressive liver failure and death before 2 years of life. Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the 11 cases where tissue was available. Seven patients had mutations in the MPV17 gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel mutations). Conclusion Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis. © 2014 Mosby Inc.
Authors & Co-Authors
Al-Hussaini, Abdulrahman Abdullah
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Faqeih, Eissa Ali
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
El-Hattab, Ayman W.
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Alfadhel, Majid
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Asery, Ali Talee
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
AlSaleem, Badr M.Rasheed
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Bakhsh, Eman
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Ali, Ashraf
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
AlAsmari, Ali Mohammed
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Lone, Khurram Sadiq
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Nahari, Ahmed Ali
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Eyaid, Wafaa M.
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Al-Balwi, Mohammed Ali
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Craig, Kate
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
Butterworth, Anna
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
He, Langping
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
Taylor, Robert William
United Kingdom, Newcastle
Wellcome Trust Centre for Mitochondrial Research
Statistics
Citations: 42
Authors: 17
Affiliations: 3
Identifiers
Doi:
10.1016/j.jpeds.2013.10.082
ISSN:
00223476
e-ISSN:
10976833
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Study Approach
Quantitative
Participants Gender
Female