2022
Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes
Tuysuz B, Alkaya D, Geyik F, Alaylıoğlu M, Kasap B, Kurugoğlu S, Akman Y, Vural M, Bilguvar K. Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes. Journal Of Medical Genetics 2022, 60: 819-826. PMID: 36543534, DOI: 10.1136/jmg-2022-108763.Peer-Reviewed Original ResearchConceptsOsteogenesis imperfectaWestern blot analysisPathogenic variantsFrameshift variantSkin fibroblast samplesExpression levelsInsulin-dependent Akt phosphorylationBlot analysisAutosomal recessive osteogenesis imperfectaWhole-exome sequencingMRNA expression levelsType 1 collagenBisphosphonate treatmentRecurrent fracturesClinical evaluationRecessive osteogenesis imperfectaCommon findingReal-time PCRMRNA expressionVertebral changesHeterogeneous groupAkt phosphorylationLong bonesBloodSkin fibroblasts
2018
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration
Schaffer AE, Breuss MW, Caglayan AO, Al-Sanaa N, Al-Abdulwahed HY, Kaymakçalan H, Yılmaz C, Zaki MS, Rosti RO, Copeland B, Baek ST, Musaev D, Scott EC, Ben-Omran T, Kariminejad A, Kayserili H, Mojahedi F, Kara M, Cai N, Silhavy JL, Elsharif S, Fenercioglu E, Barshop BA, Kara B, Wang R, Stanley V, James KN, Nachnani R, Kalur A, Megahed H, Incecik F, Danda S, Alanay Y, Faqeih E, Melikishvili G, Mansour L, Miller I, Sukhudyan B, Chelly J, Dobyns WB, Bilguvar K, Jamra RA, Gunel M, Gleeson JG. Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration. Nature Genetics 2018, 50: 1093-1101. PMID: 30013181, PMCID: PMC6072555, DOI: 10.1038/s41588-018-0166-0.Peer-Reviewed Original ResearchConceptsNeuronal migrationHuman cerebral cortexCortical neuronal migrationΒ-catenin signalingCerebral cortexPotential disease mechanismsDevelopmental brain defectsBiallelic truncating mutationsNeuronal phenotypeBiallelic lossBrain defectsBiallelic mutationsTruncating mutationsDisease mechanismsΒ-cateninPachygyriaRecessive formNeurite stabilityNeuronsFamily membersCTNNA2OveractivityPatients
2016
Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy
Madeo M, Stewart M, Sun Y, Sahir N, Wiethoff S, Chandrasekar I, Yarrow A, Rosenfeld JA, Yang Y, Cordeiro D, McCormick EM, Muraresku CC, Jepperson TN, McBeth LJ, Seidahmed MZ, Khashab H, Hamad M, Azzedine H, Clark K, Corrochano S, Wells S, Elting MW, Weiss MM, Burn S, Myers A, Landsverk M, Crotwell PL, Waisfisz Q, Wolf NI, Nolan PM, Padilla-Lopez S, Houlden H, Lifton R, Mane S, Singh BB, Falk MJ, Mercimek-Mahmutoglu S, Bilguvar K, Salih MA, Acevedo-Arozena A, Kruer MC. Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy. American Journal Of Human Genetics 2016, 98: 1249-1255. PMID: 27236917, PMCID: PMC4908178, DOI: 10.1016/j.ajhg.2016.04.008.Peer-Reviewed Original ResearchConceptsGlutamatergic neurotransmissionMovement disordersAbnormalities of glutamateEpileptic-dyskinetic encephalopathyHyperkinetic movement disordersChildhood movement disordersBiallelic pathogenic variantsChronic abnormalitiesNeurological diseasesNeurological disordersMammalian brainPathogenic variantsEpilepsyDisordersFunction mutationsNeurotransmissionAbnormalitiesMonogenic neurological diseasesOuter core proteinFRRS1LEncephalopathyEtiologyChoreoathetosisAMPAExcitatory
2015
The distinct genetic pattern of ALS in Turkey and novel mutations
Özoğuz A, Uyan Ö, Birdal G, Iskender C, Kartal E, Lahut S, Ömür Ö, Agim ZS, Eken A, Sen NE, Kavak P, Saygı C, Sapp PC, Keagle P, Parman Y, Tan E, Koç F, Deymeer F, Oflazer P, Hanağası H, Gürvit H, Bilgiç B, Durmuş H, Ertaş M, Kotan D, Akalın M, Güllüoğlu H, Zarifoğlu M, Aysal F, Döşoğlu N, Bilguvar K, Günel M, Keskin Ö, Akgün T, Özçelik H, Landers JE, Brown RH, Başak A. The distinct genetic pattern of ALS in Turkey and novel mutations. Neurobiology Of Aging 2015, 36: 1764.e9-1764.e18. PMID: 25681989, PMCID: PMC6591733, DOI: 10.1016/j.neurobiolaging.2014.12.032.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentAdultAgedAmyotrophic Lateral SclerosisAutophagy-Related ProteinsC9orf72 ProteinCell Cycle ProteinsCytoskeletal ProteinsDNA-Binding ProteinsExomeFemaleGenetic Association StudiesGuanine Nucleotide Exchange FactorsHumansIntracellular Signaling Peptides and ProteinsMaleMembrane Transport ProteinsMiddle AgedMutationNerve Tissue ProteinsNuclear ProteinsOncogene ProteinsProtein Deglycase DJ-1Protein Serine-Threonine KinasesProteinsRNA-Binding Protein FUSSequestosome-1 ProteinSuperoxide DismutaseSuperoxide Dismutase-1Transcription Factor TFIIIATRPM Cation ChannelsTurkeyUbiquitinsYoung AdultConceptsALS patientsFamilial ALS patientsSporadic ALS casesSALS patientsALS populationALS casesFamilial ALSSOD1 mutationsSQSTM1 genePatientsDistinct genetic patternsAmyotrophic lateral sclerosis mutationsExome sequencingDistinct genetic backgroundsGene mutationsSpectrum of mutationsNovel mutationsC9orf72Genetic backgroundALSMutationsPopulationSPG11TARDBP
2012
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Šestan N, Lifton RP, Günel M, Roeder K, Geschwind DH, Devlin B, State MW. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012, 485: 237-241. PMID: 22495306, PMCID: PMC3667984, DOI: 10.1038/nature10945.Peer-Reviewed Original Research
2011
Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism
Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper PB, Choi M, Crawford EL, Davis L, Wright NR, Dhodapkar RM, DiCola M, DiLullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC, McGrew AD, Meyer KA, Moffat WJ, Murdoch JD, O'Roak BJ, Ober GT, Pottenger RS, Raubeson MJ, Song Y, Wang Q, Yaspan BL, Yu TW, Yurkiewicz IR, Beaudet AL, Cantor RM, Curland M, Grice DE, Günel M, Lifton RP, Mane SM, Martin DM, Shaw CA, Sheldon M, Tischfield JA, Walsh CA, Morrow EM, Ledbetter DH, Fombonne E, Lord C, Martin CL, Brooks AI, Sutcliffe JS, Cook EH, Geschwind D, Roeder K, Devlin B, State MW. Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism. Neuron 2011, 70: 863-885. PMID: 21658581, PMCID: PMC3939065, DOI: 10.1016/j.neuron.2011.05.002.Peer-Reviewed Original ResearchAdolescentCadherinsCalcium-Binding ProteinsCell Adhesion Molecules, NeuronalChildChild Development Disorders, PervasiveChild, PreschoolChromosomes, Human, Pair 16Chromosomes, Human, Pair 7Chromosomes, Human, XDNA Copy Number VariationsFamily HealthFemaleGene DuplicationGene Expression ProfilingGenome-Wide Association StudyGenotypeHumansMaleNerve Tissue ProteinsNeural Cell Adhesion MoleculesOligonucleotide Array Sequence AnalysisPhenotypeProteinsSiblingsUbiquitin ThiolesteraseUbiquitin-Specific Peptidase 7Williams Syndrome
2010
Whole-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 mutationsPachygyriaPathogenesisHypoplasiaNeocortexNeurogenesisAbnormalitiesMalformationsMutationsFour Novel SCN1A Mutations in Turkish Patients With Severe Myoclonic Epilepsy of Infancy (SMEI)
Arlier Z, Bayri Y, Kolb LE, Erturk O, Ozturk AK, Bayrakli F, Bilguvar K, Moliterno JA, Dervent A, Demirbilek V, Yalcinkaya C, Korkmaz B, Tuysuz B, Gunel M. Four Novel SCN1A Mutations in Turkish Patients With Severe Myoclonic Epilepsy of Infancy (SMEI). Journal Of Child Neurology 2010, 25: 1265-1268. PMID: 20110217, DOI: 10.1177/0883073809357241.Peer-Reviewed Original ResearchConceptsSevere myoclonic epilepsyDravet syndromeTurkish patientsMyoclonic epilepsySCN1A geneNovel SCN1A mutationTonic-clonic seizuresRare genetic disorderUnilateral clonicSCN1A mutationsType 1SyndromeSpectrum of mutationsDisease phenotypeGenetic disordersNovel mutationsPatientsEpilepsyNovo mutationsFirst yearResponsible geneInfancyMutationsBroad spectrumAllelic heterogeneity
2007
A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly. Laboratory investigation.
Bilguvar K, Bydon M, Bayrakli F, Ercan-Sencicek AG, Bayri Y, Mason C, DiLuna ML, Seashore M, Bronen R, Lifton RP, State M, Gunel M. A novel syndrome of cerebral cavernous malformation and Greig cephalopolysyndactyly. Laboratory investigation. Journal Of Neurosurgery 2007, 107: 495-9. PMID: 18154020, DOI: 10.3171/ped-07/12/495.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleCarrier ProteinsChild, PreschoolChromosome DeletionChromosomes, Human, Pair 7Craniofacial AbnormalitiesDNAFemaleGene DosageHemangioma, Cavernous, Central Nervous SystemHeterozygoteHumansKruppel-Like Transcription FactorsNerve Tissue ProteinsOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionSyndromeZinc Finger Protein Gli3ConceptsGreig cephalopolysyndactyly syndromeCerebral cavernous malformationsDeleterious genetic variantsComparative genome hybridization analysisChromosome 7pArray-based CGHGene GLI3Distinct genesMultiple genesGenetic analysisGenomic DNANovel syndromeGenomic lesionsChromosome 7Contiguous gene syndromeQuantitative real-time polymerase chain reactionQuantitative RT-PCRGli3Hybridization analysis