Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially
Luo X, Rosenfeld J, Yamamoto S, Harel T, Zuo Z, Hall M, Wierenga K, Pastore M, Bartholomew D, Delgado M, Rotenberg J, Lewis R, Emrick L, Bacino C, Eldomery M, Coban Akdemir Z, Xia F, Yang Y, Lalani S, Lotze T, Lupski J, Lee B, Bellen H, Wangler M, . Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially. PLOS Genetics 2017, 13: e1006905. PMID: 28742085, PMCID: PMC5557584, DOI: 10.1371/journal.pgen.1006905.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnimals, Genetically ModifiedCalcium ChannelsCerebellar AtaxiaChildChild, PreschoolDrosophila melanogasterFemaleGenome, HumanGenome-Wide Association StudyHumansMaleMicroscopy, Electron, TransmissionMutation, MissenseNeurodegenerative DiseasesNeuroimagingPhenotypePoint MutationConceptsNeurodegenerative phenotypeGenomic rescue constructsS4 transmembrane segmentRescue constructTransmembrane segmentsFunction phenotypesLoss of functionMissense allelesFunction allelesWild typeGlobal developmental delayToxic gainMutant clonesDominant mutationsDevelopmental delayPoint mutationsDrosophilaFunctional impactPhenotypeQ-type voltage-dependent Ca2Early-onset developmental delayNeurological phenotypeAllelesSynaptic functionNovel variants