2024
Exploring molecular and cellular mechanisms and phenotypic characteristics of NAGLU Arg234Gly and Asp312Asn variants
Kaymakcalan Celebiler H, Barak T, Rai D, Kaya I, Erbilgin S, Cikili Uytun M, Oztop D, Gumus H, Per H, Ceylaner S, Bozkurt I, Kontaridis M, Bilguvar K, Akhun N, Kilincaslan A, Caglayan A, Erson-Omay E, Gunel M, Ercan-Sencicek A. Exploring molecular and cellular mechanisms and phenotypic characteristics of NAGLU Arg234Gly and Asp312Asn variants. Molecular Syndromology 2024, 1-15. DOI: 10.1159/000542367.Peer-Reviewed Original ResearchWhole-exome sequencingStandard Sanger sequencingMucopolysaccharidosis type IIIBExome sequencingProgressive neurodegenerative disorderConsanguineous familySanger sequencingNAGLU genePhenotypic characteristicsMagnetic resonance imagingEnzymatic assayNeurodegenerative disordersAffected individualsLoss of activityNeurodegenerative symptomsAutosomal recessive lysosomal disorderCellular mechanismsVariantsLysosomal disorderEnzymeNormal MRI findingsSequenceMPS IIIBMRI findingsType IIIB
2023
Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease
Mishra-Gorur K, Barak T, Kaulen L, Henegariu O, Jin S, Aguilera S, Yalbir E, Goles G, Nishimura S, Miyagishima D, Djenoune L, Altinok S, K. D, Viviano S, Prendergast A, Zerillo C, Ozcan K, Baran B, Sencar L, Goc N, Yarman Y, Ercan-Sencicek A, Bilguvar K, Lifton R, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2214997120. PMID: 37043537, PMCID: PMC10120005, DOI: 10.1073/pnas.2214997120.Peer-Reviewed Original ResearchConceptsWild-type proteinInherited mutationsCardiac outflow tractDevelopmental heart defectsProtein functionLack ciliaPleiotropic rolesMechanistic convergenceNeural crestCiliary defectsSomatic variantsForebrain meningesCommon originDominant mannerMutationsTRAF7ZebrafishMutantsDisparate pathologiesHeterodimerizationKnockdownGeneticsProteinCiliaCongenital heart
2022
Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities
Cali E, Suri M, Scala M, Ferla M, Alavi S, Faqeih E, Bijlsma E, Wigby K, Baralle D, Mehrjardi M, Schwab J, Platzer K, Steindl K, Hashem M, Jones M, Niyazov D, Jacober J, Littlejohn R, Weis D, Zadeh N, Rodan L, Goldenberg A, Lecoquierre F, Dutra-Clarke M, Horvath G, Young D, Orenstein N, Bawazeer S, Silfhout A, Herenger Y, Dehghani M, Seyedhassani S, Bahreini A, Nasab M, Ercan-Sencicek A, Firoozfar Z, Movahedinia M, Efthymiou S, Striano P, Karimiani E, Salpietro V, Taylor J, Redman M, Stegmann A, Laner A, Abdel-Salam G, Li M, Bengala M, Müller A, Digilio M, Rauch A, Gunel M, Titheradge H, Schweitzer D, Kraus A, Valenzuela I, McLean S, Phornphutkul C, Salih M, Begtrup A, Schnur R, Torti E, Haack T, Prada C, Alkuraya F, Houlden H, Maroofian R. Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities. Genetics In Medicine 2022, 25: 135-142. PMID: 36399134, PMCID: PMC10620944, DOI: 10.1016/j.gim.2022.09.016.Peer-Reviewed Original ResearchConceptsShort statureClinical characteristicsSyndromic neurodevelopmental disorderNeurodevelopmental disordersSevere developmental delay/intellectual disabilityPhenotypic spectrumDetailed clinical characteristicsDevelopmental delay/intellectual disabilityMain clinical characteristicsProminent supraorbital ridgesThin upper lipBroad nasal tipProtein arginine methyltransferase 7Endocrine abnormalitiesEye abnormalitiesClinical informationIntellectual developmental disabilitiesPathogenic variantsShort noseVariable findingsNatural historyBifrontal narrowingNasal tipUpper lipLower lipChildhood-Onset Neurodegeneration with Cerebellar Atrophy Syndrome: Severe Neuronal Degeneration and Cardiomyopathy with Loss of Tubulin Deglutamylase Cytosolic Carboxypeptidase 1
Samur B, Ercan-Sencicek G, Gümüş H, Gumus G, Baykan A, Caglayan A, Per H. Childhood-Onset Neurodegeneration with Cerebellar Atrophy Syndrome: Severe Neuronal Degeneration and Cardiomyopathy with Loss of Tubulin Deglutamylase Cytosolic Carboxypeptidase 1. Journal Of Pediatric Neurology 2022 DOI: 10.1055/s-0042-1749669.Peer-Reviewed Case Reports and Technical NotesClinical, demographic and genetic features of patients with congenital heart disease : A single center experience
KAYMAKCALAN H, YALCINKAYA L, NIKEREL E, YALCIN Y, DONG W, Sencıcek A. Clinical, demographic and genetic features of patients with congenital heart disease : A single center experience. Marmara Medical Journal 2022, 35: 159-163. DOI: 10.5472/marumj.1120570.Peer-Reviewed Original ResearchMutation spectrum of congenital heart disease in a consanguineous Turkish population
Dong W, Kaymakcalan H, Jin SC, Diab NS, Tanıdır C, Yalcin ASY, Ercan‐Sencicek A, Mane S, Gunel M, Lifton RP, Bilguvar K, Brueckner M. Mutation spectrum of congenital heart disease in a consanguineous Turkish population. Molecular Genetics & Genomic Medicine 2022, 10: e1944. PMID: 35481623, PMCID: PMC9184665, DOI: 10.1002/mgg3.1944.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingLaterality defectsUnique genetic architectureCongenital heart diseaseConsanguineous familyGenetic architectureCausal genesCHD genesGenome analysisHomozygous variantGenetic landscapeGenetic lesionsGenomic alterationsHeart diseaseConsanguineous populationFunction variantsRecessive variantsCHD probandsGenesType of CHDMutation spectrumStructural congenital heart diseaseVariantsCHD subjectsAdditional patientsA rare etiology of tetralogy of Fallot with pulmonary atresia: Renpenning syndrome
Kaymakçalan H, Ercan-Şençiçek AG, Cebeci AN, Dong W, Yalçın A. A rare etiology of tetralogy of Fallot with pulmonary atresia: Renpenning syndrome. The Anatolian Journal Of Cardiology 2022, 26: 149-150. PMID: 35190366, PMCID: PMC8878915, DOI: 10.5152/anatoljcardiol.2021.554.Peer-Reviewed Case Reports and Technical NotesChapter 4 Induced pluripotent stem cells for modeling Noonan, Noonan Syndrome with Multiple Lentigines, and Costello Syndromes
Ercan-Sencicek A, Chennappan S, Aromalaran K, Kontaridis M. Chapter 4 Induced pluripotent stem cells for modeling Noonan, Noonan Syndrome with Multiple Lentigines, and Costello Syndromes. 2022, 65-110. DOI: 10.1016/b978-0-323-85765-9.00007-2.ChaptersCostello syndromeNoonan syndromeInducible pluripotent stem cellsMultiple lentiginesDistinct disease characteristicsRare autosomal dominant diseaseNonhuman model systemsAutosomal dominant diseaseStem cellsAnimal model systemsPluripotent stem cellsClinical presentationDisease characteristicsTherapeutic efficacySyndromeGermline mutationsDominant diseaseNeurodevelopmental defectsRAS-PI3KAkt signalingDisease mechanismsRAS-mitogen-activated protein kinaseDisordersPatientsDifferential activation
2021
PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans
Barak T, Ristori E, Ercan-Sencicek AG, Miyagishima DF, Nelson-Williams C, Dong W, Jin SC, Prendergast A, Armero W, Henegariu O, Erson-Omay EZ, Harmancı AS, Guy M, Gültekin B, Kilic D, Rai DK, Goc N, Aguilera SM, Gülez B, Altinok S, Ozcan K, Yarman Y, Coskun S, Sempou E, Deniz E, Hintzen J, Cox A, Fomchenko E, Jung SW, Ozturk AK, Louvi A, Bilgüvar K, Connolly ES, Khokha MK, Kahle KT, Yasuno K, Lifton RP, Mishra-Gorur K, Nicoli S, Günel M. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans. Nature Medicine 2021, 27: 2165-2175. PMID: 34887573, PMCID: PMC8768030, DOI: 10.1038/s41591-021-01572-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPeptidyl-prolyl cis-transPathogenesis of IAContribution of variantsCommon genetic variantsVertebrate modelDeleterious mutationsWnt activatorAssociation studiesWhole-exome sequencingSignificant enrichmentGenetic variantsWntAngiogenesis regulatorsMutationsGene mutationsBrain angiogenesisIntracranial aneurysm ruptureJMJD6AngiogenesisCerebrovascular morphologyCerebrovascular integrityIntracerebral hemorrhageAneurysm ruptureVariantsPrevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly
Kaymakcalan H, Kaya İ, Binici N, Nikerel E, Özbaran B, Aksoy M, Erbilgin S, Özyurt G, Jahan N, Çelik D, Yararbaş K, Yalçınkaya L, Köse S, Durak S, Ercan‐Sencicek A. Prevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly. Molecular Genetics & Genomic Medicine 2021, 9: e1739. PMID: 34268892, PMCID: PMC8404225, DOI: 10.1002/mgg3.1739.Peer-Reviewed Original ResearchYAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes
Gao Y, Sun Y, Ercan-Sencicek AG, King JS, Akerberg BN, Ma Q, Kontaridis MI, Pu WT, Lin Z. YAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes. International Journal Of Molecular Sciences 2021, 22: 6649. PMID: 34206257, PMCID: PMC8268263, DOI: 10.3390/ijms22136649.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAge FactorsAnimalsCytokinesDNA-Binding ProteinsGene Expression RegulationImmunity, InnateLipopolysaccharidesMiceMice, Inbred C57BLMyocytes, CardiacSignal TransductionTEA Domain Transcription FactorsToll-Like ReceptorsTranscription FactorsYAP-Signaling ProteinsConceptsToll-like receptorsPattern recognition receptorsTLR genesPro-inflammatory cytokinesPathological stressTLR gene expressionToll-like receptor genesInnate immune responseExpression levelsHeart diseaseImmune responseHippo-YAP signalingRecognition receptorsMouse heartsYAP depletionLuciferase reporter dataReceptor geneTerminal effectorAgeReceptorsHomeostasis maintenanceMolecular mechanismsHeartExpressionExpression patternsEngineering spatial-organized cardiac organoids for developmental toxicity testing
Hoang P, Kowalczewski A, Sun S, Winston TS, Archilla AM, Lemus SM, Ercan-Sencicek AG, Gupta AR, Liu W, Kontaridis MI, Amack JD, Ma Z. Engineering spatial-organized cardiac organoids for developmental toxicity testing. Stem Cell Reports 2021, 16: 1228-1244. PMID: 33891865, PMCID: PMC8185451, DOI: 10.1016/j.stemcr.2021.03.013.Peer-Reviewed Original Research
2020
Both proliferation and lipogenesis of brown adipocytes contribute to postnatal brown adipose tissue growth in mice
Negron SG, Ercan-Sencicek AG, Freed J, Walters M, Lin Z. Both proliferation and lipogenesis of brown adipocytes contribute to postnatal brown adipose tissue growth in mice. Scientific Reports 2020, 10: 20335. PMID: 33230135, PMCID: PMC7683731, DOI: 10.1038/s41598-020-77362-x.Peer-Reviewed Original ResearchConceptsBrown adipocytesExit cell cycleDevelopmental dynamicsCell cycle activityBrown adipose tissueDifferent growth phasesMolecular mechanismsCell cycleFluorescence-activated cell sorting (FACS) analysisCell sorting (FACS) analysisBAT growthGrowth phaseEssential roleInterscapular BATCycle activityTissue growthDevelopment of BATBrown adipose tissue growthAdipocytesAdipose tissue growthInterscapular brown adipose tissueProliferationGrowthEmbryogenesisLipogenesisA patient with mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratodermia syndrome caused by AP1B1 gene variant.
Meriç R, Ercan-Sencicek AG, Uludağ Alkaya D, Şahin Y, Sar M, Bilguvar K, Tüysüz B. A patient with mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratodermia syndrome caused by AP1B1 gene variant. Clinical Dysmorphology 2020, 30: 54-57. PMID: 32969855, DOI: 10.1097/mcd.0000000000000350.Peer-Reviewed Case Reports and Technical Notes
2019
Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases
Perenthaler E, Nikoncuk A, Yousefi S, Berdowski WM, Alsagob M, Capo I, van der Linde HC, van den Berg P, Jacobs EH, Putar D, Ghazvini M, Aronica E, van IJcken WFJ, de Valk WG, Medici-van den Herik E, van Slegtenhorst M, Brick L, Kozenko M, Kohler JN, Bernstein JA, Monaghan KG, Begtrup A, Torene R, Al Futaisi A, Al Murshedi F, Mani R, Al Azri F, Kamsteeg EJ, Mojarrad M, Eslahi A, Khazaei Z, Darmiyan FM, Doosti M, Karimiani EG, Vandrovcova J, Zafar F, Rana N, Kandaswamy KK, Hertecant J, Bauer P, AlMuhaizea MA, Salih MA, Aldosary M, Almass R, Al-Quait L, Qubbaj W, Coskun S, Alahmadi KO, Hamad MHA, Alwadaee S, Awartani K, Dababo AM, Almohanna F, Colak D, Dehghani M, Mehrjardi MYV, Gunel M, Ercan-Sencicek AG, Passi GR, Cheema HA, Efthymiou S, Houlden H, Bertoli-Avella AM, Brooks AS, Retterer K, Maroofian R, Kaya N, van Ham TJ, Barakat TS. Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases. Acta Neuropathologica 2019, 139: 415-442. PMID: 31820119, PMCID: PMC7035241, DOI: 10.1007/s00401-019-02109-6.Peer-Reviewed Original ResearchConceptsUDP-glucose pyrophosphorylase genePluripotent stem cell differentiationGenetic diseasesUnfolded protein responseVisual disturbancesAltered glycogen metabolismPremature neuronal differentiationStem cell differentiationEpileptic encephalopathyUpregulated unfolded protein responseDevelopmental delayEssential genesEssential proteinsTherapy-resistant seizuresDifferentiation defectsMutant animalsStart codonMultiple lineagesProtein responseNeural stem cellsSevere epileptic encephalopathySimilar disease mechanismsSevere developmental delayShort isoformProtein absence
2018
MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome)
Rad A, Altunoglu U, Miller R, Maroofian R, James KN, Çağlayan AO, Najafi M, Stanley V, Boustany RM, Yeşil G, Sahebzamani A, Ercan-Sencicek G, Saeidi K, Wu K, Bauer P, Bakey Z, Gleeson JG, Hauser N, Gunel M, Kayserili H, Schmidts M. MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome). Journal Of Medical Genetics 2018, 56: 332. PMID: 30487245, PMCID: PMC6581149, DOI: 10.1136/jmedgenet-2018-105623.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleBrainChildChild, PreschoolConsanguinityExome SequencingFaciesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHomeodomain ProteinsHomozygoteHumansInfantLoss of Function MutationMagnetic Resonance ImagingMaleModels, MolecularNeurodevelopmental DisordersPedigreePhenotypePolymorphism, Single NucleotideProtein ConformationSyndromeConceptsScrotal agenesisCerebellar hypoplasiaCharacteristic facial gestaltHomozygous truncating variantConsanguineous familyUnrelated consanguineous familiesOphthalmological anomaliesSyndromic neurodevelopmental disorderCardinal featuresCerebello-oculoCorneal dystrophyLabioscrotal foldsTruncating variantsFunction variantsFacial gestaltExome sequencingSyndromeSimilar phenotypic featuresGenetic causeFacial dysmorphismNeurodevelopmental disordersMissense variantsVariable microcephalyNeurodevelopmental syndromeAffected individuals
2017
Novel compound heterozygous mutations in GPT2 linked to microcephaly, and intellectual developmental disability with or without spastic paraplegia
Kaymakcalan H, Yarman Y, Goc N, Toy F, Meral C, Ercan‐Sencicek A, Gunel M. Novel compound heterozygous mutations in GPT2 linked to microcephaly, and intellectual developmental disability with or without spastic paraplegia. American Journal Of Medical Genetics Part A 2017, 176: 421-425. PMID: 29226631, DOI: 10.1002/ajmg.a.38558.Peer-Reviewed Case Reports and Technical NotesConceptsNovel compound heterozygous missense variantsSpastic paraplegiaNovel compound heterozygous variantsCompound heterozygous missense variantsMissense variantsNovel compound heterozygous mutationsCompound heterozygous variantsHeterozygous missense variantsCompound heterozygous mutationsFamily membersTurkish cohortIndex patientsIntellectual developmental disabilitiesClinical phenotypeHeterozygous variantsDevelopmental delayHeterozygous mutationsAffected sisterMale siblingsUnaffected parentsFemale siblingsIntellectual disabilityDevelopmental disabilitiesSanger sequencingParaplegiaNeurogenetic analysis of childhood disintegrative disorder
Gupta AR, Westphal A, Yang DYJ, Sullivan CAW, Eilbott J, Zaidi S, Voos A, Vander Wyk BC, Ventola P, Waqar Z, Fernandez TV, Ercan-Sencicek AG, Walker MF, Choi M, Schneider A, Hedderly T, Baird G, Friedman H, Cordeaux C, Ristow A, Shic F, Volkmar FR, Pelphrey KA. Neurogenetic analysis of childhood disintegrative disorder. Molecular Autism 2017, 8: 19. PMID: 28392909, PMCID: PMC5379515, DOI: 10.1186/s13229-017-0133-0.Peer-Reviewed Original ResearchAdaptor Proteins, Signal TransducingAutism Spectrum DisorderBasic Helix-Loop-Helix Transcription FactorsBrainBrain MappingCase-Control StudiesChildChild, PreschoolChromosomes, Human, XDisease ProgressionDNA Copy Number VariationsExome SequencingFemaleGene ExpressionHumansIntellectual DisabilityMagnetic Resonance ImagingMaleMaternal InheritanceNuclear ProteinsPhenotypePolymorphism, GeneticSeverity of Illness IndexSiblingsTranscription FactorsTranscriptome
2016
Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas
Clark VE, Harmancı AS, Bai H, Youngblood MW, Lee TI, Baranoski JF, Ercan-Sencicek AG, Abraham BJ, Weintraub AS, Hnisz D, Simon M, Krischek B, Erson-Omay EZ, Henegariu O, Carrión-Grant G, Mishra-Gorur K, Durán D, Goldmann JE, Schramm J, Goldbrunner R, Piepmeier JM, Vortmeyer AO, Günel JM, Bilgüvar K, Yasuno K, Young RA, Günel M. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas. Nature Genetics 2016, 48: 1253-1259. PMID: 27548314, PMCID: PMC5114141, DOI: 10.1038/ng.3651.Peer-Reviewed Original ResearchCatalytic DomainChromosomes, Human, Pair 22Cohort StudiesDNA Mutational AnalysisEnhancer Elements, GeneticExomeGene Expression Regulation, NeoplasticGenotypeHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMeningeal NeoplasmsMeningiomaMutationNeurofibromin 2RNA Polymerase IITumor Necrosis Factor Receptor-Associated Peptides and ProteinsBiallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly
Li H, Bielas SL, Zaki MS, Ismail S, Farfara D, Um K, Rosti RO, Scott EC, Tu S, C. NC, Gabriel S, Erson-Omay EZ, Ercan-Sencicek AG, Yasuno K, Çağlayan AO, Kaymakçalan H, Ekici B, Bilguvar K, Gunel M, Gleeson JG. Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly. American Journal Of Human Genetics 2016, 99: 501-510. PMID: 27453578, PMCID: PMC4974110, DOI: 10.1016/j.ajhg.2016.07.004.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsPrimary microcephalyHuman primary microcephalyAutosomal recessive primary microcephalyNon-progressive intellectual disabilityAmino acid residuesPluripotent stem cellsMitotic cytokinesisCellular functionsGenome editingCell divisionKinase domainAbnormal cytokinesisCRISPR/Homozygous missense mutationCytokinesisKinase activityMultipolar spindlesNeural progenitorsAcid residuesFunction mutationsMissense mutationsStem cellsMultiple rolesMutations