Featured Publications
A Founder Mutation as a Cause of Cerebral Cavernous Malformation in Hispanic Americans
Günel M, Awad I, Finberg K, Anson J, Steinberg G, Batjer H, Kopitnik T, Morrison L, Giannotta S, Nelson-Williams C, Lifton R. A Founder Mutation as a Cause of Cerebral Cavernous Malformation in Hispanic Americans. New England Journal Of Medicine 1996, 334: 946-951. PMID: 8596595, DOI: 10.1056/nejm199604113341503.Peer-Reviewed Original ResearchConceptsCavernous malformationsCerebral cavernous malformationsSporadic casesFamilial diseaseSame mutationSporadic cavernous malformationsDevelopment of symptomsHispanic AmericansCerebral hemorrhageVascular diseaseAsymptomatic carriersHigh prevalenceClinical casesMalformationsDiseaseFounder mutationPatientsAge dependenceAffected membersKindredsMarkersMexican descentEthnic groupsMutationsSame alleleWhole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations
Bilgüvar K, Öztürk A, Louvi A, Kwan KY, Choi M, Tatlı B, Yalnızoğlu D, Tüysüz B, Çağlayan A, Gökben S, Kaymakçalan H, Barak T, Bakırcıoğlu M, Yasuno K, Ho W, Sanders S, Zhu Y, Yılmaz S, Dinçer A, Johnson MH, Bronen RA, Koçer N, Per H, Mane S, Pamir MN, Yalçınkaya C, Kumandaş S, Topçu M, Özmen M, Šestan N, Lifton RP, State MW, Günel M. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 2010, 467: 207-210. PMID: 20729831, PMCID: PMC3129007, DOI: 10.1038/nature09327.Peer-Reviewed Original ResearchConceptsAbnormal cortical developmentWD repeat domain 62 (WDR62) geneSevere brain malformationsWhole-exome sequencingBrain abnormalitiesBrain malformationsCortical developmentMolecular pathogenesisCerebellar hypoplasiaWDR62 mutationsEmbryonic neurogenesisDiagnostic classificationMicrocephaly genesSmall family sizeGenetic heterogeneityWide spectrumRecessive mutationsPachygyriaPathogenesisHypoplasiaNeocortexNeurogenesisAbnormalitiesMalformationsMutationsMutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors
Mishra-Gorur K, Çağlayan AO, Schaffer AE, Chabu C, Henegariu O, Vonhoff F, Akgümüş GT, Nishimura S, Han W, Tu S, Baran B, Gümüş H, Dilber C, Zaki MS, Hossni HA, Rivière JB, Kayserili H, Spencer EG, Rosti RÖ, Schroth J, Per H, Çağlar C, Çağlar Ç, Dölen D, Baranoski JF, Kumandaş S, Minja FJ, Erson-Omay EZ, Mane SM, Lifton RP, Xu T, Keshishian H, Dobyns WB, C. N, Šestan N, Louvi A, Bilgüvar K, Yasuno K, Gleeson JG, Günel M. Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors. Neuron 2014, 84: 1226-1239. PMID: 25521378, PMCID: PMC5024344, DOI: 10.1016/j.neuron.2014.12.014.Peer-Reviewed Original ResearchConceptsComplex cerebral malformationsCerebral cortical malformationsMicrotubule-severing enzyme kataninExome sequencing analysisMitotic spindle formationDrosophila optic lobeCerebral malformationsPatient-derived fibroblastsCell cycle progression delayCortical malformationsMotor neuronsComplex malformationsMicrotubule-associated proteinsCortical developmentReduced cell numberOptic lobeRegulatory subunitBrain developmentCatalytic subunitDeleterious mutationsSpindle formationSupernumerary centrosomesArborization defectsMalformationsHuman phenotypes
2016
Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation detected by whole exome sequencing.
Yılmaz B, Toktaş ZO, Akakın A, Işık S, Bilguvar K, Kılıç T, Günel M. Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation detected by whole exome sequencing. Journal Of Neurosurgery 2016, 126: 1879-1883. PMID: 27611203, DOI: 10.3171/2016.6.jns16665.Peer-Reviewed Original ResearchConceptsBrain arteriovenous malformationsHereditary hemorrhagic telangiectasiaWhole-exome sequencingArteriovenous malformationsExome sequencingWhole-exome sequencing analysisSpinal arteriovenous malformationsDiagnostic classification schemesExome sequencing analysisComprehensive genomic characterizationConclusion Study resultsCranial MRIDirect Sanger sequencingHemorrhagic telangiectasiaBlood samplesFamilial occurrenceHeterozygous mutationsACVRL1 mutationsPatientsThree SiblingsFourth siblingVariant segregationSanger sequencingMalformationsSiblings
2014
Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration
Louvi A, Nishimura S, Günel M. Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration. Development 2014, 141: 1404-1415. PMID: 24595293, PMCID: PMC3943187, DOI: 10.1242/dev.093526.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCell MovementCell ProliferationCyclin-Dependent Kinase 5FemaleHemangioma, Cavernous, Central Nervous SystemIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMice, TransgenicNeocortexNeural Stem CellsNeurogliaPregnancyRho GTP-Binding ProteinsRhoA GTP-Binding ProteinSignal TransductionConceptsCerebral cavernous malformation 3Neuronal migrationCerebral cavernous malformationsRadial glia progenitorsCell non-autonomous functionCerebrovascular disordersPyramidal neuronsCortical plateLaminar positioningSubventricular zoneCortical developmentCavernous malformationsRadial gliaLoss of functionNascent neuronsNeuronal morphologySevere malformationsGlia progenitorsNeural progenitorsNeuronsNon-autonomous functionsMalformationsRhoA pathwayPossible interactionsGlia
2013
Mutations in LAMB1 Cause Cobblestone Brain Malformation without Muscular or Ocular Abnormalities
Radmanesh F, Caglayan AO, Silhavy JL, Yilmaz C, Cantagrel V, Omar T, Rosti B, Kaymakcalan H, Gabriel S, Li M, Šestan N, Bilguvar K, Dobyns WB, Zaki MS, Gunel M, Gleeson JG. Mutations in LAMB1 Cause Cobblestone Brain Malformation without Muscular or Ocular Abnormalities. American Journal Of Human Genetics 2013, 92: 468-474. PMID: 23472759, PMCID: PMC3591846, DOI: 10.1016/j.ajhg.2013.02.005.Peer-Reviewed Original ResearchConceptsBrain malformationsCongenital muscular dystrophyOcular abnormalitiesPial surfaceWhite matter signal abnormalitiesNeuronal migration disordersRadial glial cellsPial basement membraneLaminin subunit beta-1Brainstem hypoplasiaFirst cortical layerSignal abnormalitiesCerebellar dysplasiaGlial cellsMigration disordersMuscular abnormalitiesOccipital encephaloceleCortical layersBrain diseasesAbnormalitiesHomozygous deleterious mutationMalformationsBeta 1Muscular dystrophyAffected individuals
2002
KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein
Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, Nelson-Williams C, Lifton RP. KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10677-10682. PMID: 12140362, PMCID: PMC125011, DOI: 10.1073/pnas.122354499.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAortaCattleCells, CulturedCentral Nervous System Vascular MalformationsChlorocebus aethiopsCOS CellsEndothelium, VascularGene ExpressionMicrotubule-Associated ProteinsMicrotubulesMitosisMolecular Sequence DataMutagenesisPrecipitin TestsProto-Oncogene ProteinsRadiographyTubulinConceptsCerebral cavernous malformationsCavernous malformationsCerebral cavernous malformation lesionsMicrotubule-associated proteinsProtein-1 alphaAutosomal dominant diseaseEndothelial tube formationCerebral hemorrhageCerebral capillariesEndothelial cellsDominant diseaseMalformationsTube formationPlus endsSite of cytokinesisSpindle pole bodyEvidence of interactionGene 1Possible roleCell-matrix interactionsKRIT1Late phaseEnds of microtubulesEndothelial cell shapePole body
1996
Genetic Heterogeneity of Inherited Cerebral Cavernous Malformation
Günel M, Awad I, Finberg K, Steinberg G, Craig H, Cepeda O, Nelson-Williams C, Lifton R. Genetic Heterogeneity of Inherited Cerebral Cavernous Malformation. Neurosurgery 1996, 38: 1265-1271. DOI: 10.1227/00006123-199606000-00059.Peer-Reviewed Original ResearchConceptsGenetic analysisCauses of CCMsCerebral cavernous malformationsHuman chromosome 7Second geneIndependent inheritanceMutant geneChromosome 7Genetic markersGenesLong armGenetic heterogeneityMutationsCavernous malformationsInheritanceFamilyAutosomal dominant transmissionClinical featuresGenetic testingDominant transmissionKindredsMarkersNon-Hispanic familiesMalformationsDisordersGenetic heterogeneity of inherited cerebral cavernous malformation.
Günel M, Awad I, Finberg K, Steinberg G, Craig H, Cepeda O, Carol N, Lifton R. Genetic heterogeneity of inherited cerebral cavernous malformation. Neurosurgery 1996, 38: 1265-71. PMID: 8727164, DOI: 10.1097/00006123-199606000-00059.Peer-Reviewed Original ResearchConceptsGenetic analysisCauses of CCMsCerebral cavernous malformationsHuman chromosome 7Second geneIndependent inheritanceMutant geneChromosome 7Genetic markersGenesLong armGenetic heterogeneityMutationsCavernous malformationsInheritanceFamilyAutosomal dominant transmissionClinical featuresGenetic testingDominant transmissionKindredsMarkersNon-Hispanic familiesMalformationsDisorders