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Leigh syndrome: One disorder, more than 75 monogenic causes
Author(s) -
Lake Nicole J.,
Compton Alison G.,
Rahman Shamima,
Thorburn David R.
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24551
Subject(s) - etiology , disease , leigh disease , mitochondrial disease , genetic heterogeneity , phenotype , mitochondrial dna , genetics , genotype phenotype distinction , biology , nuclear gene , gene , bioinformatics , medicine , pathology
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