2019
Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases
Liu W, Pajusalu S, Lake NJ, Zhou G, Ioannidis N, Mittal P, Johnson NE, Weihl CC, Williams BA, Albrecht DE, Rufibach LE, Lek M. Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases. Genetics In Medicine 2019, 21: 2512-2520. PMID: 31105274, DOI: 10.1038/s41436-019-0544-8.Peer-Reviewed Original ResearchConceptsMuscular dystrophyLimb-girdle muscular dystrophyClinical trialsGene-level mechanismsLower incidencePossible underdiagnosisGeneral populationEpidemiological studiesEpidemiology dataPrevalence estimatesGenetic subtypesMuscle diseaseLGMD subtypesDisease prevalencePrevalenceRecessive diseaseSubtypesPublic sequencing databasesDiseaseTrialsLGMDDystrophyHeterogeneous categorySequencing databasesLeigh syndrome caused by mutations in MTFMT is associated with a better prognosis
Hayhurst H, de Coo I, Piekutowska‐Abramczuk D, Alston C, Sharma S, Thompson K, Rius R, He L, Hopton S, Ploski R, Ciara E, Lake N, Compton A, Delatycki M, Verrips A, Bonnen P, Jones S, Morris A, Shakespeare D, Christodoulou J, Wesol‐Kucharska D, Rokicki D, Smeets H, Pronicka E, Thorburn D, Gorman G, McFarland R, Taylor R, Ng Y. Leigh syndrome caused by mutations in MTFMT is associated with a better prognosis. Annals Of Clinical And Translational Neurology 2019, 6: 515-524. PMID: 30911575, PMCID: PMC6414492, DOI: 10.1002/acn3.725.Peer-Reviewed Original ResearchConceptsPathogenic variantsLeigh syndromeSubcortical white matter abnormalitiesNew casesFrequent initial manifestationLast clinical reviewRetrospective cohort studyBasal ganglia changesWhite matter abnormalitiesRespiratory chain deficiencyBi-allelic pathogenic variantsMitochondrial methionyl-tRNA formyltransferaseMolecular genetic findingsMilder clinical phenotypeInitial manifestationBrainstem lesionsCohort studyMedian ageBetter prognosisChain deficiencyMotor symptomsClinical reviewDisease progressionMultiple respiratory chain deficiencyMuscle biopsy
2017
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome
Lake N, Webb B, Stroud D, Richman T, Ruzzenente B, Compton A, Mountford H, Pulman J, Zangarelli C, Rio M, Boddaert N, Assouline Z, Sherpa M, Schadt E, Houten S, Byrnes J, McCormick E, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo S, Mootha V, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk M, Metodiev M, Thorburn D. Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. American Journal Of Human Genetics 2017, 101: 239-254. PMID: 28777931, PMCID: PMC5544391, DOI: 10.1016/j.ajhg.2017.07.005.Peer-Reviewed Original ResearchConceptsSmall mitoribosomal subunitMitoribosomal subunitHuman oxidative phosphorylation (OXPHOS) systemMitochondrial protein translationOxidative phosphorylation systemMitochondrial translation defectQuantitative proteomic analysisSpecific cellular pathwaysLeigh syndromeLentiviral-mediated expressionMitoribosomal proteinsMitochondrial ribosomesOXPHOS subunitsMitochondrial translationOXPHOS defectsProtein translationMitochondrial DNATranslation defectsUnrelated familiesProteomic analysisPhosphorylation systemQuantitative proteomicsCellular pathwaysProtein subunitsSubunit proteinsATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism
Desai R, Frazier A, Durigon R, Patel H, Jones A, Rosa I, Lake N, Compton A, Mountford H, Tucker E, Mitchell A, Jackson D, Sesay A, Di Re M, van den Heuvel L, Burke D, Francis D, Lunke S, McGillivray G, Mandelstam S, Mochel F, Keren B, Jardel C, Turner A, Andrews P, Smeitink J, Spelbrink J, Heales S, Kohda M, Ohtake A, Murayama K, Okazaki Y, Lombès A, Holt I, Thorburn D, Spinazzola A. ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism. Brain 2017, 140: 1595-1610. PMID: 28549128, PMCID: PMC5445257, DOI: 10.1093/brain/awx094.Peer-Reviewed Original ResearchConceptsATAD3A geneHigh-throughput sequencing technologyIntegration of mitochondriaMitochondrial DNA organizationCholesterol homeostasisCellular cholesterol homeostasisSingle nucleotide polymorphism arrayMitochondrial DNA abnormalitiesNiemann-Pick type C diseaseNucleotide polymorphism arrayWhole-exome sequencing dataDNA organizationExome sequencing dataMitochondrial DNACausal genesCholesterol metabolismGenomic analysisGenomic rearrangementsSequencing technologiesHigh homologySequencing dataType C diseaseDrug-induced perturbationsGene cluster deletionsGenes