0000000000202607

AUTHOR

Philip L. Beales

showing 4 related works from this author

Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.

2012

Background Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathway, as being responsible for this syndrome. Methods We sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based on facial dysmorphism and brain anomalies. Results Seven mutations were identified at the KIF7 locus in these five cases, six of which are novel. We describe the first four compound heterozygous cases. In all patients, the diagnosis was suspecte…

MaleAcrocallosal SyndromeKinesinsDysgenesisFetusIntellectual DisabilityGeneticsmedicineHumansCraniofacialHypertelorismGenetics (clinical)PolydactylyCorpus Callosum Agenesisbusiness.industryAnatomyMiddle Agedmedicine.diseaseAcrocallosal syndromeHypoplasiaPolydactylyPhenotypeAgenesisChild PreschoolMutationFemalemedicine.symptomAgenesis of Corpus CallosumbusinessJournal of medical genetics
researchProduct

CiliaCarta: An integrated and validated compendium of ciliary genes

2019

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse…

ProteomicsSensory ReceptorsNematodaSocial SciencesCiliopathiesBiochemistrySensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Transcriptome0302 clinical medicineAnimal CellsPsychologyRETINAL PHOTORECEPTOR CELLSExomeNeurons0303 health sciences030302 biochemistry & molecular biologyEukaryotaGenomicsPRIMARY CILIUMthecilium3. Good healthNucleic acidsGenetic interferenceOsteichthyesMedicineEpigeneticsCellular Structures and OrganellesCellular Typesproteomic databasesSensory Receptor CellsScienceeducationCiliary genesLEBER CONGENITAL AMAUROSISGenomics03 medical and health sciencesGeneticsCiliaCaenorhabditis elegansIDENTIFICATIONMUTATIONSEmbryosciliaOrganismsBiology and Life SciencesBayes TheoremMolecular Sequence Annotationmedicine.diseaseInvertebratesFishciliary proteomeAnimal StudiesCaenorhabditisGene expressionembryos030217 neurology & neurosurgeryDevelopmental BiologyNeurosciencePhotoreceptorsCandidate geneEmbryologyOligonucleotidesMorpholinoDatabase and Informatics MethodsRNA interferenceBayesian classifierTRANSITION ZONEZebrafishAntisense OligonucleotidesZebrafishGeneticsMultidisciplinarySpectrometric Identification of ProteinsProteomic DatabasesNucleotidesCiliumQStable Isotope Labeling by Amino Acids in Cell CultureRphotoreceptorsMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]Animal ModelsPhenotypeINTRAFLAGELLAR TRANSPORTDIFFERENTIATIONPhenotypeExperimental Organism SystemsCaenorhabditis ElegansVertebratesSensory PerceptionResearch ArticleSignal TransductionEXPRESSIONStable isotope labeling by amino acids in cell cultureComputational biologyBiologyResearch and Analysis MethodsSOLUTE-CARRIER-PROTEINModel OrganismsmedicineAnimalsdata integration030304 developmental biologyAfferent NeuronsReproducibility of ResultsCell Biologyzebrafishbiology.organism_classificationCiliopathyRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]Biological DatabasesCellular NeuroscienceRNAOSCP1CiliaCartaPLoS ONE
researchProduct

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

2015

Item does not contain fulltext Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequen…

PRPF31Pregnancy ProteinsInbred C57BLCiliopathiesMiceImmunologicCerebellumDatabases GeneticEye AbnormalitiesNon-U.S. Gov'tZebrafishExome sequencingMice KnockoutGeneticsResearch Support Non-U.S. Gov'tCiliumHigh-Throughput Nucleotide SequencingMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]GenomicsKidney Diseases CysticPhenotypeKidney DiseasesRNA InterferenceAbnormalitiesMultipleFunctional genomicsCiliary Motility DisordersGenetic MarkersEllis-Van Creveld SyndromeKnockoutJeune syndromeOther Research Radboud Institute for Molecular Life Sciences [Radboudumc 0]BiologyResearch SupportTransfectionRetinaArticlewhole-genome siRNA screenJoubert syndromeN.I.H.DatabasesCysticreverse geneticsResearch Support N.I.H. ExtramuralGeneticCerebellar DiseasesJoubert syndromeCiliogenesisSuppressor FactorsJournal ArticleSuppressor Factors ImmunologicmedicineAnimalsHumansAbnormalities MultipleGenetic Predisposition to DiseasePhotoreceptor CellsCiliaGenetic TestingCaenorhabditis elegansExtramuralMembrane ProteinsProteinsReproducibility of ResultsCell Biologymedicine.diseaseMice Inbred C57BLCytoskeletal ProteinsCiliopathyRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]HEK293 CellsMutationciliopathiesGenome-Wide Association StudyNature Cell Biology
researchProduct

Non-essential role for cilia in coordinating precise alignment of lens fibres

2016

The primary cilium, a microtubule-based organelle found in most cells, is a centre for mechano-sensing fluid movement and cellular signalling, notably through the Hedgehog pathway. We recently found that each lens fibre cell has an apically situated primary cilium that is polarised to the side of the cell facing the anterior pole of the lens. The direction of polarity is similar in neighbouring cells so that in the global view, lens fibres exhibit planar cell polarity (PCP) along the equatorial-anterior polar axis. Ciliogenesis has been associated with the establishment of PCP, although the exact relationship between PCP and the role of cilia is still controversial. To test the hypothesis t…

0301 basic medicineEmbryologyBBSomeBiologyArticle03 medical and health sciences0302 clinical medicineIntraflagellar transportMicrotubuleCiliogenesisLens CrystallineAnimalsBasal bodyLens placodeCiliaCells CulturedMice KnockoutTumor Suppressor ProteinsCiliumCell PolarityEpithelial CellsAnatomyCell biologyCytoskeletal Proteins030104 developmental biologyFiber cellMicrotubule-Associated Proteins030217 neurology & neurosurgeryDevelopmental BiologyMechanisms of Development
researchProduct