2019
A patient with homozygous nonsense variants in two Leigh syndrome disease genes: Distinguishing a dual diagnosis from a hypomorphic protein‐truncating variant
Lake N, Formosa L, Stroud D, Ryan M, Calvo S, Mootha V, Morar B, Procopis P, Christodoulou J, Compton A, Thorburn D. A patient with homozygous nonsense variants in two Leigh syndrome disease genes: Distinguishing a dual diagnosis from a hypomorphic protein‐truncating variant. Human Mutation 2019, 40: 893-898. PMID: 30981218, PMCID: PMC6661004, DOI: 10.1002/humu.23753.Peer-Reviewed Original ResearchConceptsProtein-truncating variantsCI assemblyC-terminusLeigh syndromeMutant proteinsKnockout cellsDisease genesUncharacterized variantsHypomorphic effectPathogenic variantsLeigh-like syndromeMitochondrial diseaseWhole-exome sequencingGenomic criteriaFunctional studiesAmino acidsGenesTIMMDC1Homozygous nonsense variantPatient's clinical phenotypeClinical phenotypeExome sequencingNonsense variantMedical GeneticsDual diagnosis
2016
Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder
Nafisinia M, Guo Y, Dang X, Li J, Chen Y, Zhang J, Lake N, Gold W, Riley L, Thorburn D, Keating B, Xu X, Hakonarson H, Christodoulou J. Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder. JIMD Reports 2016, 32: 117-124. PMID: 27344648, PMCID: PMC5362551, DOI: 10.1007/8904_2016_541.Peer-Reviewed Original ResearchLeigh syndromeCompound heterozygous mutationsLate-onset Leigh syndromeWhole-exome sequencingWhole exome sequencing identifiesAmino acid substitution p.Putaminal abnormalitiesSpongiform lesionsCapillary proliferationMitochondrial respiratory chain functionLactate peakExome sequencing identifiesPatientsBrain tissuePatient muscleSyndromeBrain MRSHeterozygous mutationsExome sequencingPathogenic effectsProtein expressionRespiratory chain functionLaboratory evaluationSubstitution p.Significant reduction