2020
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D’Angio’ M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C, Snow A, Dalgard C, Milner J, Vinh D, Mogensen T, Marr N, Spaan A, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli M, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton R, Zhang S, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice C, Abel L, Notarangelo L, Cobat A, Su H, Casanova J, Foti G, Bellani G, Citerio G, Contro E, Pesci A, Valsecchi M, Cazzaniga M, Abad J, Aguilera-Albesa S, Akcan O, Darazam I, Aldave J, Ramos M, Nadji S, Alkan G, Allardet-Servent J, Allende L, Alsina L, Alyanakian M, Amador-Borrero B, Amoura Z, Antolí A, Arslan S, Assant S, Auguet T, Azot A, Bajolle F, Baldolli A, Ballester M, Feldman H, Barrou B, Beurton A, Bilbao A, Blanchard-Rohner G, Blanco I, Blandinières A, Blazquez-Gamero D, Bloomfield M, Bolivar-Prados M, Borie R, Bosteels C, Bousfiha A, Bouvattier C, Boyarchuk O, Bueno M, Bustamante J, Cáceres Agra J, Calimli S, Capra R, Carrabba M, Casasnovas C, Caseris M, Castelle M, Castelli F, de Vera M, Castro M, Catherinot E, Chalumeau M, Charbit B, Cheng M, Clavé P, Clotet B, Codina A, Colkesen F, Çölkesen F, Colobran R, Comarmond C, Dalmau D, Darley D, Dauby N, Dauger S, de Pontual L, Dehban A, Delplancq G, Demoule A, Diehl J, Dobbelaere S, Durand S, Eldars W, Elgamal M, Elnagdy M, Emiroglu M, Erdeniz E, Aytekin S, Euvrard R, Evcen R, Fabio G, Faivre L, Falck A, Fartoukh M, Faure M, Arquero M, Flores C, Francois B, Fumadó V, Fusco F, Solis B, Gaussem P, Gil-Herrera J, Gilardin L, Alarcon M, Girona-Alarcón M, Goffard J, Gok F, González-Montelongo R, Guerder A, Gul Y, Guner S, Gut M, Hadjadj J, Haerynck F, Halwani R, Hammarström L, Hatipoglu N, Hernandez-Brito E, Heijmans C, Holanda-Peña M, Horcajada J, Hoste L, Hoste E, Hraiech S, Humbert L, Iglesias A, Íñigo-Campos A, Jamme M, Arranz M, Jordan I, Jorens P, Kanat F, Kapakli H, Kara I, Karbuz A, Yasar K, Keles S, Demirkol Y, Klocperk A, Król Z, Kuentz P, Kwan Y, Lagier J, Lambrecht B, Lau Y, Le Bourgeois F, Leo Y, Lopez R, Leung D, Levin M, Levy M, Lévy R, Li Z, Linglart A, Loeys B, Lorenzo-Salazar J, Louapre C, Lubetzki C, Luyt C, Lye D, Mansouri D, Marjani M, Pereira J, Martin A, Pueyo D, Martinez-Picado J, Marzana I, Mathian A, Matos L, Matthews G, Mayaux J, Mège J, Melki I, Meritet J, Metin O, Meyts I, Mezidi M, Migeotte I, Millereux M, Mirault T, Mircher C, Mirsaeidi M, Melián A, Martinez A, Morange P, Mordacq C, Morelle G, Mouly S, Muñoz-Barrera A, Naesens L, Nafati C, Neves J, Ng L, Medina Y, Cuadros E, Ocejo-Vinyals J, Orbak Z, Oualha M, Özçelik T, Pan-Hammarström Q, Parizot C, Pascreau T, Paz-Artal E, Pellegrini S, de Diego R, Philippe A, Philippot Q, Planas-Serra L, Ploin D, Poissy J, Poncelet G, Pouletty M, Quentric P, Raoult D, Rebillat A, Reisli I, Ricart P, Richard J, Rivet N, Rivière J, Blanch G, Rodrigo C, Rodriguez-Gallego C, Rodríguez-Palmero A, Romero C, Rothenbuhler A, Rozenberg F, Ruiz del Prado M, Riera J, Sanchez O, Sánchez-Ramón S, Schluter A, Schmidt M, Schweitzer C, Scolari F, Sediva A, Seijo L, Sene D, Senoglu S, Seppänen M, Ilovich A, Shahrooei M, Slabbynck H, Smadja D, Sobh A, Moreno X, Solé-Violán J, Soler C, Soler-Palacín P, Stepanovskiy Y, Stoclin A, Taccone F, Tandjaoui-Lambiotte Y, Taupin J, Tavernier S, Terrier B, Thumerelle C, Tomasoni G, Toubiana J, Alvarez J, Trouillet-Assant S, Troya J, Tucci A, Ursini M, Uzunhan Y, Vabres P, Valencia-Ramos J, Van Braeckel E, Van de Velde S, Van Den Rym A, Van Praet J, Vandernoot I, Vatansev H, Vélez-Santamaria V, Viel S, Vilain C, Vilaire M, Vincent A, Voiriot G, Vuotto F, Yosunkaya A, Young B, Yucel F, Zannad F, Zatz M, Belot A, Bole-Feysot C, Lyonnet S, Masson C, Nitschke P, Pouliet A, Schmitt Y, Tores F, Zarhrate M, Abel L, Andrejak C, Angoulvant F, Bachelet D, Basmaci R, Behillil S, Beluze M, Benkerrou D, Bhavsar K, Bompart F, Bouadma L, Bouscambert M, Caralp M, Cervantes-Gonzalez M, Chair A, Coelho A, Couffignal C, Couffin-Cadiergues S, D’Ortenzio E, Da Silveira C, Debray M, Deplanque D, Descamps D, Desvallées M, Diallo A, Diouf A, Dorival C, Dubos F, Duval X, Eloy P, Enouf V, Esperou H, Esposito-Farese M, Etienne M, Ettalhaoui N, Gault N, Gaymard A, Ghosn J, Gigante T, Gorenne I, Guedj J, Hoctin A, Hoffmann I, Jaafoura S, Kafif O, Kaguelidou F, Kali S, Khalil A, Khan C, Laouénan C, Laribi S, Le M, Le Hingrat Q, Le Mestre S, Le Nagard H, Lescure F, Lévy Y, Levy-Marchal C, Lina B, Lingas G, Lucet J, Malvy D, Mambert M, Mentré F, Mercier N, Meziane A, Mouquet H, Mullaert J, Neant N, Noret M, Pages J, Papadopoulos A, Paul C, Peiffer-Smadja N, Petrov-Sanchez V, Peytavin G, Picone O, Puéchal O, Rosa-Calatrava M, Rossignol B, Rossignol P, Roy C, Schneider M, Semaille C, Mohammed N, Tagherset L, Tardivon C, Tellier M, Téoulé F, Terrier O, Timsit J, Trioux T, Tual C, Tubiana S, van der Werf S, Vanel N, Veislinger A, Visseaux B, Wiedemann A, Yazdanpanah Y, Alavoine L, Amat K, Behillil S, Bielicki J, Bruijning P, Burdet C, Caumes E, Charpentier C, Coignard B, Costa Y, Couffin-Cadiergues S, Damond F, Dechanet A, Delmas C, Descamps D, Duval X, Ecobichon J, Enouf V, Espérou H, Frezouls W, Houhou N, Ilic-Habensus E, Kafif O, Kikoine J, Le Hingrat Q, Lebeaux D, Leclercq A, Lehacaut J, Letrou S, Lina B, Lucet J, Malvy D, Manchon P, Mandic M, Meghadecha M, Motiejunaite J, Nouroudine M, Piquard V, Postolache A, Quintin C, Rexach J, Roufai L, Terzian Z, Thy M, Tubiana S, van der Werf S, Vignali V, Visseaux B, Yazdanpanah Y, van Agtmael M, Algera A, van Baarle F, Bax D, Beudel M, Bogaard H, Bomers M, Bos L, Botta M, de Brabander J, de Bree G, Brouwer M, de Bruin S, Bugiani M, Bulle E, Chouchane O, Cloherty A, Elbers P, Fleuren L, Geerlings S, Geerts B, Geijtenbeek T, Girbes A, Goorhuis B, Grobusch M, Hafkamp F, Hagens L, Hamann J, Harris V, Hemke R, Hermans S, Heunks L, Hollmann M, Horn J, Hovius J, de Jong M, Koning R, van Mourik N, Nellen J, Paulus F, Peters E, van der Poll T, Preckel B, Prins J, Raasveld J, Reijnders T, Schinkel M, Schultz M, Schuurman A, Sigaloff K, Smit M, Stijnis C, Stilma W, Teunissen C, Thoral P, Tsonas A, van der Valk M, Veelo D, Vlaar A, de Vries H, van Vugt M, Wiersinga W, Wouters D, Zwinderman A, van de Beek D, Abel L, Aiuti A, Al Muhsen S, Al-Mulla F, Anderson M, Arias A, Feldman H, Bogunovic D, Bolze A, Bondarenko A, Bousfiha A, Brodin P, Bryceson Y, Bustamante C, Butte M, Casari G, Chakravorty S, Christodoulou J, Cirulli E, Condino-Neto A, Cooper M, Dalgard C, David A, DeRisi J, Desai M, Drolet B, Espinosa S, Fellay J, Flores C, Franco J, Gregersen P, Haerynck F, Hagin D, Halwani R, Heath J, Henrickson S, Hsieh E, Imai K, Itan Y, Karamitros T, Kisand K, Ku C, Lau Y, Ling Y, Lucas C, Maniatis T, Mansouri D, Marodi L, Meyts I, Milner J, Mironska K, Mogensen T, Morio T, Ng L, Notarangelo L, Novelli A, Novelli G, O’Farrelly C, Okada S, Ozcelik T, de Diego R, Planas A, Prando C, Pujol A, Quintana-Murci L, Renia L, Renieri A, Rodríguez-Gallego C, Sancho-Shimizu V, Sankaran V, Barrett K, Shahrooei M, Snow A, Soler-Palacín P, Spaan A, Tangye S, Turvey S, Uddin F, Uddin M, van de Beek D, Vazquez S, Vinh D, von Bernuth H, Washington N, Zawadzki P, Su H, Casanova J, Jing H, Tung W, Luthers C, Bauman B, Shafer S, Zheng L, Zhang Z, Kubo S, Chauvin S, Meguro K, Shaw E, Lenardo M, Lack J, Karlins E, Hupalo D, Rosenberger J, Sukumar G, Wilkerson M, Zhang X. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 2020, 370: eabd4570. PMID: 32972995, PMCID: PMC7857407, DOI: 10.1126/science.abd4570.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAllelesAsymptomatic InfectionsBetacoronavirusChildChild, PreschoolCoronavirus InfectionsCOVID-19FemaleGenetic LociGenetic Predisposition to DiseaseHumansInfantInterferon Regulatory Factor-7Interferon Type ILoss of Function MutationMaleMiddle AgedPandemicsPneumonia, ViralReceptor, Interferon alpha-betaSARS-CoV-2Toll-Like Receptor 3Young AdultConceptsLife-threatening COVID-19 pneumoniaCOVID-19 pneumoniaSevere acute respiratory syndrome coronavirus 2Type I interferon immunityAcute respiratory syndrome coronavirus 2Life-threatening COVID-19Respiratory syndrome coronavirus 2Toll-like receptor 3Inborn errorsSyndrome coronavirus 2Coronavirus disease 2019Interferon regulatory factor 7Years of ageAutosomal-dominant deficiencySARS-CoV-2Rare variantsRegulatory factor 7Patients 17Clinical outcomesCoronavirus 2Silent infectionSevere infectionsDisease 2019Benign infectionReceptor 3
2018
Loss of Protocadherin‐12 Leads to Diencephalic‐Mesencephalic Junction Dysplasia Syndrome
Guemez‐Gamboa A, Çağlayan AO, Stanley V, Gregor A, Zaki M, Saleem SN, Musaev D, McEvoy‐Venneri J, Belandres D, Akizu N, Silhavy JL, Schroth J, Rosti RO, Copeland B, Lewis SM, Fang R, Issa MY, Per H, Gumus H, Bayram AK, Kumandas S, Akgumus GT, Erson‐Omay E, Yasuno K, Bilguvar K, Heimer G, Pillar N, Shomron N, Weissglas‐Volkov D, Porat Y, Einhorn Y, Gabriel S, Ben‐Zeev B, Gunel M, Gleeson JG. Loss of Protocadherin‐12 Leads to Diencephalic‐Mesencephalic Junction Dysplasia Syndrome. Annals Of Neurology 2018, 84: 638-647. PMID: 30178464, PMCID: PMC6510237, DOI: 10.1002/ana.25327.Peer-Reviewed Original ResearchConceptsBrainstem malformationDysplasia syndromeEndothelial cellsBiallelic mutationsAutosomal recessive malformationSuch pathogenic variantsCharacteristic clinical presentationPatient-derived induced pluripotent stem cellsWhite matter tractsAnn NeurolAppendicular spasticityBrain calcificationClinical presentationPoor outcomeAxial hypotoniaPsychomotor disabilityProgressive microcephalyTract defectsPathogenic variantsPhenotypic spectrumPatientsCraniofacial dysmorphismBrain imagingNeural precursorsProtein expression
2016
Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder
Tărlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell 2016, 167: 1481-1494.e18. PMID: 27912058, PMCID: PMC5554935, DOI: 10.1016/j.cell.2016.11.013.Peer-Reviewed Original ResearchConceptsBlood-brain barrierBrain barrierBrain amino acid profilesLarge neutral amino acid transporterAutism spectrum disorderAdult mutant miceBranched-chain amino acid (BCAA) catabolic pathwaySevere neurological abnormalitiesNeutral amino acid transporterIntracerebroventricular administrationNeurological syndromeNeurological abnormalitiesNeurological conditionsSpectrum disorderSLC7A5 geneMotor delayAmino acid transportAmino acid transportersMutant miceNormal levelsBrain functionHuman brain functionEndothelial cellsHomozygous mutationCauses of ASDBiallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly
Jerber J, Zaki MS, Al-Aama JY, Rosti RO, Ben-Omran T, Dikoglu E, Silhavy JL, Caglar C, Musaev D, Albrecht B, Campbell KP, Willer T, Almuriekhi M, Çağlayan A, Vajsar J, Bilgüvar K, Ogur G, Jamra R, Günel M, Gleeson JG. Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. American Journal Of Human Genetics 2016, 99: 1181-1189. PMID: 27773428, PMCID: PMC5097947, DOI: 10.1016/j.ajhg.2016.09.007.Peer-Reviewed Original ResearchConceptsCongenital muscular dystrophyCobblestone lissencephalyOvermigration of neuronsBiallelic mutationsMuscular dystrophyTMTC3Affected individualsWalker-Warburg syndromeMembrane componentsSevere brain malformationsBasement membrane componentsFukuyama congenital muscular dystrophyMuscle creatine phosphokinaseEye defectsMutationsGenesRecessive formGenetic disordersGlial cellsMinimal eyeMuscle involvementCortical dysplasiaBrain malformationsEye anomaliesCreatine phosphokinaseTwo locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles
Timberlake AT, Choi J, Zaidi S, Lu Q, Nelson-Williams C, Brooks ED, Bilguvar K, Tikhonova I, Mane S, Yang JF, Sawh-Martinez R, Persing S, Zellner EG, Loring E, Chuang C, Galm A, Hashim PW, Steinbacher DM, DiLuna ML, Duncan CC, Pelphrey KA, Zhao H, Persing JA, Lifton RP. Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles. ELife 2016, 5: e20125. PMID: 27606499, PMCID: PMC5045293, DOI: 10.7554/elife.20125.Peer-Reviewed Original ResearchConceptsMidline craniosynostosisInhibitor of BMPCommon variantsDamaging de novoGenetic interactionsPhenotypic variationParent-offspring triosEpistatic interactionsGenetic basisOsteoblast differentiationLocus inheritanceAnalysis of linkageDe novoExome sequencingIncomplete penetranceMutationsTransmitted mutationsLoss-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
2014
Paediatric 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 childhoodHomozygous loss of DIAPH1 is a novel cause of microcephaly in humans
Ercan-Sencicek AG, Jambi S, Franjic D, Nishimura S, Li M, El-Fishawy P, Morgan TM, Sanders SJ, Bilguvar K, Suri M, Johnson MH, Gupta AR, Yuksel Z, Mane S, Grigorenko E, Picciotto M, Alberts AS, Gunel M, Šestan N, State MW. Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans. European Journal Of Human Genetics 2014, 23: 165-172. PMID: 24781755, PMCID: PMC4297910, DOI: 10.1038/ejhg.2014.82.Peer-Reviewed Original ResearchConceptsCell divisionFamily-based linkage analysisLinkage analysisRho effector proteinsLinear actin filamentsMaintenance of polarityMitotic cell divisionHigh-throughput sequencingRare genetic variantsHuman neuronal precursor cellsParametric multipoint linkage analysisActivation of GTPNeuronal precursor cellsFormin familyMammalian DiaphanousEffector proteinsMultipoint linkage analysisSpindle formationActin filamentsNonsense alterationWhole-exome sequencingHuman pathologiesNeuroepithelial cellsGenetic variantsHomozygous loss
2011
The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis
Bakircioglu M, Carvalho OP, Khurshid M, Cox JJ, Tuysuz B, Barak T, Yilmaz S, Caglayan O, Dincer A, Nicholas AK, Quarrell O, Springell K, Karbani G, Malik S, Gannon C, Sheridan E, Crosier M, Lisgo SN, Lindsay S, Bilguvar K, Gergely F, Gunel M, Woods CG. The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis. American Journal Of Human Genetics 2011, 88: 523-535. PMID: 21529752, PMCID: PMC3146716, DOI: 10.1016/j.ajhg.2011.03.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCentrosomeCerebral CortexChild, PreschoolDNA Mutational AnalysisEpithelial CellsExonsFemaleGenetic LinkageHeLa CellsHomozygoteHumansInfantMaleMiceMicrocephalyMicrotubule-Associated ProteinsMutationNeural Stem CellsNeurogenesisNeuronsPhenotypePregnancyRNA, MessengerTransfectionConceptsCortical laminationPatient-derived cell linesDistinct homozygous mutationsProfound mental retardationCerebral cortexCerebral cortex neurogenesisMouse embryonic brainNeuron productionBrain scansPostmortem dataEmbryonic brainNeural precursorsHomozygous mutationNeuroepithelial cellsNeurogenesisPatient cellsMental retardationExtreme microcephalyAffected individualsEarly neurogenesisCell linesT mutationPakistani originBrainTurkish family