Review
Leigh syndrome: One disorder, more than 75 monogenic causes
Nicole J. Lake MSc,
Alison G. Compton PhD,
Shamima Rahman MD, PhD,
David R. Thorburn PhD,
Nicole J. Lake MSc
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorAlison G. Compton PhD
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorShamima Rahman MD, PhD
Mitochondrial Research Group, Genetics and Genomic Medicine, Institute of Child Health, University College London and Metabolic Unit, Great Ormond Street Hospital, London, United Kingdom
Search for more papers by this authorCorresponding Author
David R. Thorburn PhD
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Victorian Clinical Genetic Services, Royal Children's Hospital, Melbourne, Victoria, Australia
Address correspondence to Dr Thorburn, Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, Victoria, 3052, Australia. E-mail: [email protected]Search for more papers by this authorNicole J. Lake MSc,
Alison G. Compton PhD,
Shamima Rahman MD, PhD,
David R. Thorburn PhD,
Nicole J. Lake MSc
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorAlison G. Compton PhD
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorShamima Rahman MD, PhD
Mitochondrial Research Group, Genetics and Genomic Medicine, Institute of Child Health, University College London and Metabolic Unit, Great Ormond Street Hospital, London, United Kingdom
Search for more papers by this authorCorresponding Author
David R. Thorburn PhD
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Victorian Clinical Genetic Services, Royal Children's Hospital, Melbourne, Victoria, Australia
Address correspondence to Dr Thorburn, Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, Victoria, 3052, Australia. E-mail: [email protected]Search for more papers by this authorAbstract
Leigh syndrome is the most common pediatric presentation of mitochondrial disease. This neurodegenerative disorder is genetically heterogeneous, and to date pathogenic mutations in >75 genes have been identified, encoded by 2 genomes (mitochondrial and nuclear). More than one-third of these disease genes have been characterized in the past 5 years alone, reflecting the significant advances made in understanding its etiological basis. We review the diverse biochemical and genetic etiology of Leigh syndrome and associated clinical, neuroradiological, and metabolic features that can provide clues for diagnosis. We discuss the emergence of genotype–phenotype correlations, insights gleaned into the molecular basis of disease, and available therapeutic options. Ann Neurol 2016;79:190–203
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