2024
High-throughput assays to assess variant effects on disease
Ma K, Gauthier L, Cheung F, Huang S, Lek M. High-throughput assays to assess variant effects on disease. Disease Models & Mechanisms 2024, 17: dmm050573. PMID: 38940340, PMCID: PMC11225591, DOI: 10.1242/dmm.050573.Peer-Reviewed Original ResearchConceptsDeep mutational scanningGenetic variantsRare disease diagnosticsRare genetic variantsDisease mechanismsHigh-throughput assaySequencing effortsInvestigation of variantsMutational scanningModel cell lineVariant effectsMolecular toolsCell linesCell survival rateFunctional assaysDrug resistanceDisease diagnosticsDisease-relevant assaysVariantsClinical case reportBiological mechanismsAssayCase reportClinical reportsSurvival rate
2023
P154 The generation of a GNE myopathy patient-derived biobank enables the study of disease-relevant cellular phenotypes across multiple pathogenic variants
Koczwara K, Lake N, Huang S, DeSimone A, Pajusalu S, Branford K, Hallak D, Woodman K, Xu J, Lek A, Best H, Habib A, Avelar J, Martin V, Mozaffar T, Shieh P, Weisleder N, Lek M. P154 The generation of a GNE myopathy patient-derived biobank enables the study of disease-relevant cellular phenotypes across multiple pathogenic variants. Neuromuscular Disorders 2023, 33: s138. DOI: 10.1016/j.nmd.2023.07.286.Peer-Reviewed Original ResearchPathogenic mutationsCRISPR/Cas9 knockoutDisease-relevant cell typesSialic acid biosynthesis pathwayCellular disease modelsMyogenic cell lineCell linesGNE myopathy patientsPatient-derived cell linesGNE activityWhole-genome sequencingGNE proteinPathogenic variantsBiosynthesis pathwayDisease-relevant cellular phenotypesCellular functionsMyogenic lineageCellular phenotypesRNA sequencingBifunctional enzymeGenome sequencingMultiple pathogenic variantsReduced enzymatic activitySkeletal muscle atrophyMyopathy patients