Mutations in mitochondrial DNA causing tubulointerstitial kidney disease

Connor, Thomas M., Hoer, Simon, Mallett, Andrew, Gale, Daniel P., Gomez-Duran, Aurora, Posse, Viktor, Antrobus, Robin, Moreno, Pablo, Sciacovelli, Marco, Frezza, Christian, Duff, Jennifer, Sheerin, Neil S., Sayer, John A., Ashcroft, Margaret, Wiesener, Michael S., Hudson, Gavin, Gustafsson, Claes M., Chinnery, Patrick F. and Maxwell, Patrick H. (2017) Mutations in mitochondrial DNA causing tubulointerstitial kidney disease. PLoS Genetics, 13 3: . doi:10.1371/journal.pgen.1006620


Author Connor, Thomas M.
Hoer, Simon
Mallett, Andrew
Gale, Daniel P.
Gomez-Duran, Aurora
Posse, Viktor
Antrobus, Robin
Moreno, Pablo
Sciacovelli, Marco
Frezza, Christian
Duff, Jennifer
Sheerin, Neil S.
Sayer, John A.
Ashcroft, Margaret
Wiesener, Michael S.
Hudson, Gavin
Gustafsson, Claes M.
Chinnery, Patrick F.
Maxwell, Patrick H.
Title Mutations in mitochondrial DNA causing tubulointerstitial kidney disease
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7404
1553-7390
Publication date 2017-03-01
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1006620
Open Access Status DOI
Volume 13
Issue 3
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2018
Language eng
Formatted abstract
Tubulointerstitial kidney disease is an important cause of progressive renal failure whose aetiology is incompletely understood. We analysed a large pedigree with maternally inherited tubulointerstitial kidney disease and identified a homoplasmic substitution in the control region of the mitochondrial genome (m.547A>T). While mutations in mtDNA coding sequence are a well recognised cause of disease affecting multiple organs, mutations in the control region have never been shown to cause disease. Strikingly, our patients did not have classical features of mitochondrial disease. Patient fibroblasts showed reduced levels of mitochondrial tRNAPhe, tRNALeu1 and reduced mitochondrial protein translation and respiration. Mitochondrial transfer demonstrated mitochondrial transmission of the defect and in vitro assays showed reduced activity of the heavy strand promoter. We also identified further kindreds with the same phenotype carrying a homoplasmic mutation in mitochondrial tRNAPhe(m.616T>C). Thus mutations in mitochondrial DNA can cause maternally inherited renal disease, likely mediated through reduced function of mitochondrial tRNAPhe.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Medicine Publications
 
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