Journal article
Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a Leigh syndrome patient
DK Miller, MJ Menezes, C Simons, LG Riley, ST Cooper, SM Grimmond, DR Thorburn, J Christodoulou, RJ Taft
Plos One | PUBLIC LIBRARY SCIENCE | Published : 2014
Open access
Abstract
Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative disorder, the genetics of which is frequently difficult to resolve. Rapid determination of the genetic etiology of LS in a 5-year-old girl facilitated inclusion in Edison Pharmaceutical's phase 2B clinical trial of EPI-743. SNP-arrays and high-coverage whole exome sequencing were performed on the proband, both parents and three unaffected siblings. Subsequent multi-tissue targeted high-depth mitochondrial sequencing was performed using custom long-range PCR amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was interrogated by spectrophotometric enzyme assays and Western Blot. No putatively caus..
View full abstractGrants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
The authors thank Illumina Inc. for their support of this project, and the Queensland Center for Medical Genomics and the IMB Sequencing Core for their assistance. This research was supported by National Health and Medical Research Council of Australia (NHMRC) Project Grant 1026891, and a University of Queensland Foundation Research Excellence Award to RJT. MM is an Australian Mitochondrial Diseases Foundation (AMDF) Postgraduate Research Scholar. DRT is an NHMRC Principal Research Fellow. The authors thank Wendy Fagan for assistance with enzyme assays and are grateful to the Crane and Perkins families for their generous financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.