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 ruptureVariants
2018
Genotype–phenotype investigation of 35 patients from 11 unrelated families with camptodactyly–arthropathy–coxa vara–pericarditis (CACP) syndrome
Yilmaz S, Alkaya D, Kasapçopur Ö, Barut K, Akdemir ES, Celen C, Youngblood MW, Yasuno K, Bilguvar K, Günel M, Tüysüz B. Genotype–phenotype investigation of 35 patients from 11 unrelated families with camptodactyly–arthropathy–coxa vara–pericarditis (CACP) syndrome. Molecular Genetics & Genomic Medicine 2018, 6: 230-248. PMID: 29397575, PMCID: PMC5902402, DOI: 10.1002/mgg3.364.Peer-Reviewed Original ResearchConceptsCoxa vara-pericarditis (CACP) syndromeCoxa varaCommon childhood rheumatic diseaseIncreased pain levelSevere hip involvementChildhood rheumatic diseasesJuvenile idiopathic arthritisDevelopmental coxa varaRare autosomal recessive conditionYears of ageUnrelated familiesWhole-exome sequencingAutosomal recessive conditionHip involvementIdiopathic arthritisMost patientsPain levelsRadiological findingsPleural effusionJoint involvementNoninflammatory arthropathyRheumatic diseasesNovel genomic alterationsFirst symptomsCACP syndrome
2017
ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features
Çağlayan AO, Sezer RG, Kaymakçalan H, Ulgen E, Yavuz T, Baranoski JF, Bozaykut A, Harmanci AS, Yalcin Y, Youngblood MW, Yasuno K, Bilgüvar K, Gunel M. ALPK3 gene mutation in a patient with congenital cardiomyopathy and dysmorphic features. Molecular Case Studies 2017, 3: a001859. PMID: 28630369, PMCID: PMC5593152, DOI: 10.1101/mcs.a001859.Peer-Reviewed Original ResearchConceptsNovel homozygous frameshift mutationWk of gestationHomozygous pathogenic variantNovel disease-causing genesPhenotypic featuresHomozygous frameshift mutationWhole-exome sequencingHeterozygous family membersUnrelated consanguineous familiesEchocardiographic examinationDisease groupPrimary cardiomyopathyMale infantHypertrophic cardiomyopathyRoutine diagnostic toolCardiac diseaseCardiac abnormalitiesMale fetusesCardiomyopathyPathogenic variantsGenetic testingDysmorphic featuresGene mutationsPast historyDisease-causing genesExome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination
Vilarinho S, Erson-Omay E, Mitchell-Richards K, Cha C, Nelson-Williams C, Harmancı AS, Yasuno K, Günel M, Taddei TH. Exome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination. Journal Of Hepatology 2017, 67: 186-191. PMID: 28323122, PMCID: PMC5497691, DOI: 10.1016/j.jhep.2017.03.009.Peer-Reviewed Original ResearchConceptsAdenoma-carcinoma transitionHepatocellular adenomaBrain metastasesHepatocellular carcinomaVascular invasionTumor thrombusCatenin beta 1Rare benign liver tumorMultifocal hepatic lesionsAcute abdominal painBenign liver tumorsPeripheral blood leucocytesSomatic mutationsWhole-exome sequencingParaffin-embedded samplesBrain disseminationAbdominal painLeft hepatectomyMajor complicationsLiver diseaseSpontaneous hemorrhageLeft lobeDisease progressionBlood leucocytesLiver tumorsLongitudinal analysis of treatment-induced genomic alterations in gliomas
Erson-Omay EZ, Henegariu O, Omay SB, Harmancı AS, Youngblood MW, Mishra-Gorur K, Li J, Özduman K, Carrión-Grant G, Clark VE, Çağlar C, Bakırcıoğlu M, Pamir MN, Tabar V, Vortmeyer AO, Bilguvar K, Yasuno K, DeAngelis LM, Baehring JM, Moliterno J, Günel M. Longitudinal analysis of treatment-induced genomic alterations in gliomas. Genome Medicine 2017, 9: 12. PMID: 28153049, PMCID: PMC5290635, DOI: 10.1186/s13073-017-0401-9.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsChromosome AberrationsCombined Modality TherapyDisease ProgressionDNA Mismatch RepairDNA Mutational AnalysisDNA, NeoplasmExomeFemaleGeneral SurgeryGenome, HumanGenomicsGlioblastomaHumansImmunotherapyLongitudinal StudiesMiddle AgedMutationNeoplasm Recurrence, LocalPrecision MedicineRadiotherapyTreatment OutcomeConceptsWhole-exome sequencingMismatch repair deficiencyImmune checkpoint inhibitionMalignant brain tumorsMolecular changesLongitudinal analysisMedian survivalCheckpoint inhibitionSubsequent recurrenceMaximal resectionStandard treatmentBackgroundGlioblastoma multiformeBrain tumorsTumor-normal pairsFavorable responsePrimary GBMIndividual tumorsConclusionsOur studyPrecision therapyPersonalized treatmentGenomic profilingRepair deficiencyGenomic alterationsGenomic profilesTherapy
2016
A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP
Çağlayan AO, Tüysüz B, Coşkun S, Quon J, Harmancı AS, Baranoski JF, Baran B, Erson-Omay EZ, Henegariu O, Mane SM, Bilgüvar K, Yasuno K, Günel M. A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP. Journal Of Human Genetics 2016, 61: 395-403. PMID: 26740239, PMCID: PMC4880488, DOI: 10.1038/jhg.2015.160.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Ketoglutarate-Dependent Dioxygenase FTOApoptosisBiopsyChild, PreschoolCholesterol Ester Transfer ProteinsComputational BiologyConsanguinityDNA Copy Number VariationsDNA Mutational AnalysisExomeFemaleGene ExpressionGene Expression ProfilingGenetic Association StudiesGenotypeHigh-Throughput Nucleotide SequencingHomozygoteHumansMutation, MissensePhenotypeTranscriptome
2014
Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations
Caglayan AO, Baranoski JF, Aktar F, Han W, Tuysuz B, Guzel A, Guclu B, Kaymakcalan H, Aktekin B, Akgumus GT, Murray PB, Erson-Omay EZ, Caglar C, Bakircioglu M, Sakalar YB, Guzel E, Demir N, Tuncer O, Senturk S, Ekici B, Minja FJ, Šestan N, Yasuno K, Bilguvar K, Caksen H, Gunel M. Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations. Pediatric Neurology 2014, 51: 806-813.e8. PMID: 25456301, PMCID: PMC5056964, DOI: 10.1016/j.pediatrneurol.2014.08.025.Peer-Reviewed Original ResearchConceptsBrain malformationsKnobloch syndromeCentral nervous system malformationsExpanding Clinical SpectrumStructural brain abnormalitiesStructural brain malformationsNervous system malformationsHuman cerebral cortexHuman cortical developmentWhole-exome sequencingConfirmatory Sanger sequencingCase seriesClinical presentationCerebral cortexClinical spectrumBrain abnormalitiesOcular abnormalitiesSystem malformationsClinical utilityCortical developmentImmunohistochemical analysisRare diseaseCOL18A1 mutationsBrain developmentPatientsPaediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations
Vilarinho S, Erson-Omay EZ, Harmanci AS, Morotti R, Carrion-Grant G, Baranoski J, Knisely AS, Ekong U, Emre S, Yasuno K, Bilguvar K, Günel M. Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations. Journal Of Hepatology 2014, 61: 1178-1183. PMID: 25016225, DOI: 10.1016/j.jhep.2014.07.003.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBase SequenceBeta CateninCarcinoma, HepatocellularCholestasis, IntrahepaticDNA, NeoplasmFemaleGerm-Line MutationHumansInfantLiver NeoplasmsMolecular Sequence DataMutationMutation, MissenseNF-E2-Related Factor 2Sequence Homology, Amino AcidConceptsBile salt export pumpWhole-exome sequencingHepatocellular carcinomaMonths of ageNFE2L2 mutationsABCB11 mutationsSomatic CTNNB1Background liver parenchymaPediatric hepatocellular carcinomaNew onsetSomatic driver mutationsBSEP expressionLiver parenchymaHCC tissuesHepatocellular carcinogenesisWES analysisExport pumpDriver mutationsCTNNB1 mutationsExome sequencingChild's diagnosisClonality analysisGermline DNAPossible genetic basisEarly childhood
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 mutationsPachygyriaPathogenesisHypoplasiaNeocortexNeurogenesisAbnormalitiesMalformationsMutations