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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+Genet
2017 ; 13
(3
): e1006620
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Mutations in mitochondrial DNA causing tubulointerstitial kidney disease
#MMPMID28267784
Connor TM
; Hoer S
; Mallett A
; Gale DP
; Gomez-Duran A
; Posse V
; Antrobus R
; Moreno P
; Sciacovelli M
; Frezza C
; Duff J
; Sheerin NS
; Sayer JA
; Ashcroft M
; Wiesener MS
; Hudson G
; Gustafsson CM
; Chinnery PF
; Maxwell PH
PLoS Genet
2017[Mar]; 13
(3
): e1006620
PMID28267784
show ga
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.