2024
Reply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in 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, Rai D, Viviano S, Prendergast A, Zerillo C, Ozcan K, Baran B, Sencar L, Goc N, Yarman Y, Ercan-encicek A, Bilguvar K, Lifton R, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Reply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in congenital heart disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319578121. PMID: 38466853, PMCID: PMC10963000, DOI: 10.1073/pnas.2319578121.Commentaries, Editorials and Letters
2023
LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility
Hwang J, Chai P, Nawaz S, Choi J, Lopez-Giraldez F, Hussain S, Bilguvar K, Mane S, Lifton R, Ahmad W, Zhang K, Chung J. LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. ELife 2023, 12: rp90095. PMID: 38091523, PMCID: PMC10721216, DOI: 10.7554/elife.90095.Peer-Reviewed Original ResearchSuper-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas
Youngblood M, Erson-Omay Z, Li C, Najem H, Coșkun S, Tyrtova E, Montejo J, Miyagishima D, Barak T, Nishimura S, Harmancı A, Clark V, Duran D, Huttner A, Avşar T, Bayri Y, Schramm J, Boetto J, Peyre M, Riche M, Goldbrunner R, Amankulor N, Louvi A, Bilgüvar K, Pamir M, Özduman K, Kilic T, Knight J, Simon M, Horbinski C, Kalamarides M, Timmer M, Heimberger A, Mishra-Gorur K, Moliterno J, Yasuno K, Günel M. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications 2023, 14: 6279. PMID: 37805627, PMCID: PMC10560290, DOI: 10.1038/s41467-023-41926-y.Peer-Reviewed Original ResearchTRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions
Almousa H, Lewis S, Bakhtiari S, Nordlie S, Pagnozzi A, Magee H, Efthymiou S, Heim J, Cornejo P, Zaki M, Anwar N, Maqbool S, Rahman F, Neilson D, Vemuri A, Jin S, Yang X, Heidari A, van Gassen K, Trimouille A, Thauvin-Robinet C, Liu J, Bruel A, Tomoum H, Shata M, Hashem M, Toosi M, Karimiani E, Yeşil G, Lingappa L, Baruah D, Ebrahimzadeh F, Van-Gils J, Faivre L, Zamani M, Galehdari H, Sadeghian S, Shariati G, Mohammad R, van der Smagt J, Qari A, Vincent J, Innes A, Dursun A, Özgül R, Akar H, Bilguvar K, Mignot C, Keren B, Raveli C, Burglen L, Afenjar A, Kaat L, van Slegtenhorst M, Alkuraya F, Houlden H, Padilla-Lopez S, Maroofian R, Sacher M, Kruer M. TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions. Brain 2023, 147: 311-324. PMID: 37713627, PMCID: PMC10766242, DOI: 10.1093/brain/awad301.Peer-Reviewed Original ResearchToward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing
Erdogan O, Özkaya Ş, Erzik C, Bilguvar K, Arga K, Bayraklı F. Toward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing. OMICS A Journal Of Integrative Biology 2023, 27: 426-433. PMID: 37669106, DOI: 10.1089/omi.2023.0117.Peer-Reviewed Original ResearchConceptsTreatment optionsWhole-exome sequencingPrecision/personalized medicineExome sequencingLimited treatment optionsGenetic alterationsPersonalized medicinePotential therapeutic targetAggressive brain tumorTumor tissue samplesPoor prognosisGBM patientsTargetable pathwaysBrain tumorsTherapeutic targetLarger studyMolecular findingsNeurosurgical oncologyGenomic profilingPatientsPersonalized therapyMolecular profilingAkt/GlioblastomaPrecision oncologyPleiotropic 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 heartInborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
Lee D, Le Pen J, Yatim A, Dong B, Aquino Y, Ogishi M, Pescarmona R, Talouarn E, Rinchai D, Zhang P, Perret M, Liu Z, Jordan I, Bozdemir S, Bayhan G, Beaufils C, Bizien L, Bisiaux A, Lei W, Hasan M, Chen J, Gaughan C, Asthana A, Libri V, Luna J, Jaffré F, Hoffmann H, Michailidis E, Moreews M, Seeleuthner Y, Bilguvar K, Mane S, Flores C, Zhang Y, Arias A, Bailey R, Schlüter A, Milisavljevic B, Bigio B, Le Voyer T, Materna M, Gervais A, Moncada-Velez M, Pala F, Lazarov T, Levy R, Neehus A, Rosain J, Peel J, Chan Y, Morin M, Pino-Ramirez R, Belkaya S, Lorenzo L, Anton J, Delafontaine S, Toubiana J, Bajolle F, Fumadó V, DeDiego M, Fidouh N, Rozenberg F, Pérez-Tur J, Chen S, Evans T, Geissmann F, Lebon P, Weiss S, Bonnet D, Duval X, Pan-Hammarström Q, Planas A, Meyts I, Haerynck F, Pujol A, Sancho-Shimizu V, Dalgard C, Bustamante J, Puel A, Boisson-Dupuis S, Boisson B, Maniatis T, Zhang Q, Bastard P, Notarangelo L, Béziat V, de Diego R, Rodriguez-Gallego C, Su H, Lifton R, Jouanguy E, Cobat A, Alsina L, Keles S, Haddad E, Abel L, Belot A, Quintana-Murci L, Rice C, Silverman R, Zhang S, Casanova J, Alavoine L, Behillil S, Burdet C, Charpentier C, Dechanet A, Descamps D, Duval X, Ecobichon J, Enouf V, Frezouls W, Houhou N, Kafif O, Lehacaut J, Letrou S, Lina B, Lucet J, Manchon P, Nouroudine M, Piquard V, Quintin C, Thy M, Tubiana S, van der Werf S, Vignali V, Visseaux B, Yazdanpanah Y, Chahine A, Waucquier N, Migaud M, Deplanque D, Djossou F, Mergeay-Fabre M, Lucarelli A, Demar M, Bruneau L, Gérardin P, Maillot A, Payet C, Laviolle B, Laine F, Paris C, Desille-Dugast M, Fouchard J, Malvy D, Nguyen D, Pistone T, Perreau P, Gissot V, Le Goas C, Montagne S, Richard L, Chirouze C, Bouiller K, Desmarets M, Meunier A, Lefèvre B, Jeulin H, Legrand K, Lomazzi S, Tardy B, Gagneux-Brunon A, Bertholon F, Botelho-Nevers E, Christelle K, Nicolas L, Roufai L, Amat K, Couffin-Cadiergues S, Espérou H, Hendou S, Abel L, Abolhassani H, Aguilera-Albesa S, Aiuti A, Akcan O, Akcay N, Alkan G, Alkhater S, Allende L, Alper Y, Amenzoui N, Anderson M, Arkin L, Aubart M, Avramenko I, Aydemir Ş, Aydin Z, Aytekin C, Aytekin G, Aytekin S, Bando S, Beland K, Belkaya S, Biggs C, Aburto A, Blanchard-Rohner G, Blázquez-Gamero D, Bloomfield M, Bogunovic D, Bondarenko A, Borghesi A, Bousfiha A, Boyarchuk O, Brodin P, Bryceson Y, Bucciol G, Calcaterra V, Casari G, Cavalcanti A, Celik J, Chrousos G, Colobran R, Condino-Neto A, Conti F, Cooper M, Coskuner T, Cyrus C, D’Auria E, Delafontaine S, Drolet B, Duramaz B, Zein L, Elnagdy M, Emiroglu M, Erdeniz E, Fabi M, Feldman H, Fellay J, Fencl F, Filippatos F, Freiss J, Fremuth J, Gagro A, Garcia-Solis B, Vergine G, González-Montelongo R, Gul Y, Gülhan B, Gultekin S, Gut M, Halwani R, Hammarström L, Hatipoğlu N, Heath J, Henrickson S, Hernandez-Brito E, Hoffman I, Hoste L, Hsieh E, Íñigo-Campos A, Itan Y, Jabandziev P, Kandemir B, Kanık-Yüksek S, Kapakli H, Karbuz A, Kasapcopur O, Kechiche R, Demirkol Y, Kilic O, Hansen S, Klocperk A, Lau Y, Lebl J, Lorenzo-Salazar J, Lucas C, Maglorius M, Marque L, Medina Y, Melián A, Mentis A, Pato M, Michos A, Milner J, Mogensen T, Muñoz-Barrera A, Nepesov S, Neves J, Ng A, Ng L, Novelli A, Novelli G, Oz F, Ocejo-Viñals J, Okada S, Orbak Z, Kilic A, Ouair H, Öz Ş, Özçelik T, Özkan E, Parlakay A, Pato C, Paz-Artal E, Pelham S, Pellier I, Philippot Q, Planas-Serra L, Plassart S, Pokorna P, Polat M, Poli C, Prando C, Renia L, Rivière J, Rodríguez-Palmero A, Roussel L, Rubio-Rodriguez L, Salifu M, Sasek L, Sasia L, Scherbina A, Schmitt E, Sediva A, Sevketoglu E, Slaba K, Slaby O, Sobh A, Solé-Violán J, Soler-Palacin P, De Somer L, Sözeri B, Spaan A, Stepanovskiy Y, Tangye S, Tanir G, Tatsi E, Thorball C, Torun S, Turvey S, Uddin M, Uyar E, Valencia-Ramos J, Van Den Rym A, Vatansev H, de Vera M, Vermeulen F, Vinh D, Volokha A, von Bernuth H, Wouters C, Yahşi A, Yarar V, Yesilbas O, Yıldız M, Zatz M, Zawadzki P, Zuccotti G, Zhang S, Casanova J. Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children. Science 2023, 379: eabo3627. PMID: 36538032, PMCID: PMC10451000, DOI: 10.1126/science.abo3627.Peer-Reviewed Original ResearchConceptsOAS-RNase LInflammatory syndromeCytokine productionInflammatory cytokinesSARS-CoV-2-related multisystem inflammatory syndromeCytosolic double-stranded RNAMultisystem inflammatory syndromeRig-I deficiencySuppress cytokine productionPrimary myeloid cellsRNase LMonocytic cell lineAutosomal recessive deficiencyMyeloid cellsMononuclear phagocytesUnrelated childrenInborn errorsRecessive deficiencyDeficient cellsProtein deficiencyCOVID-19Cell linesCytokinesSyndromeDouble-stranded RNA
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 fibroblastsAssessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents
Oliveira CR, Niccolai LM, Sheikha H, Elmansy L, Kalinich CC, Grubaugh ND, Shapiro ED, Billig K, Breban M, Brito A, Earnest R, Fauver J, Koch T, Ott I, Petrone M, Vogels C, Pham K, Tikhonova I, Castaldi C, Mane S, Bilguvar K, De Kumar B, Ferguson D, Kerantzas N, Landry M, Peaper D, Schulz W. Assessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents. JAMA Network Open 2022, 5: e220935. PMID: 35238933, PMCID: PMC8895259, DOI: 10.1001/jamanetworkopen.2022.0935.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionCase-control studyVaccine effectivenessBNT162b2 vaccineSARS-CoV-2Medical recordsAsymptomatic SARS-CoV-2 infectionBNT162b2 COVID-19 vaccineRetrospective case-control studyRT-PCR test resultsSARS-CoV-2 testUS adolescentsReverse transcription polymerase chain reaction testConditional logistic regression modelsTranscription polymerase chain reaction testDoses of vaccineControl participantsClinical trial populationsRelevant clinical dataCase participantsCOVID-19 vaccinePositive test resultsChain reaction testCounty of residenceNegative test resultsCenters for Mendelian Genomics: A decade of facilitating gene discovery
Baxter SM, Posey JE, Lake NJ, Sobreira N, Chong JX, Buyske S, Blue EE, Chadwick LH, Coban-Akdemir ZH, Doheny KF, Davis CP, Lek M, Wellington C, Jhangiani SN, Gerstein M, Gibbs RA, Lifton RP, MacArthur DG, Matise TC, Lupski JR, Valle D, Bamshad MJ, Hamosh A, Mane S, Nickerson DA, Consortium C, Adams M, Aguet F, Akay G, Anderson P, Antonescu C, Arachchi H, Atik M, Austin-Tse C, Babb L, Bacus T, Bahrambeigi V, Balasubramanian S, Bayram Y, Beaudet A, Beck C, Belmont J, Below J, Bilguvar K, Boehm C, Boerwinkle E, Boone P, Bowne S, Brand H, Buckingham K, Byrne A, Calame D, Campbell I, Cao X, Carvalho C, Chander V, Chang J, Chao K, Chinn I, Clarke D, Collins R, Cummings B, Dardas Z, Dawood M, Delano K, DiTroia S, Doddapaneni H, Du H, Du R, Duan R, Eldomery M, Eng C, England E, Evangelista E, Everett S, Fatih J, Felsenfeld A, Francioli L, Frazar C, Fu J, Gamarra E, Gambin T, Gan W, Gandhi M, Ganesh V, Garimella K, Gauthier L, Giroux D, Gonzaga-Jauregui C, Goodrich J, Gordon W, Griffith S, Grochowski C, Gu S, Gudmundsson S, Hall S, Hansen A, Harel T, Harmanci A, Herman I, Hetrick K, Hijazi H, Horike-Pyne M, Hsu E, Hu J, Huang Y, Hurless J, Jahl S, Jarvik G, Jiang Y, Johanson E, Jolly A, Karaca E, Khayat M, Knight J, Kolar J, Kumar S, Lalani S, Laricchia K, Larkin K, Leal S, Lemire G, Lewis R, Li H, Ling H, Lipson R, Liu P, Lovgren A, López-Giráldez F, MacMillan M, Mangilog B, Mano S, Marafi D, Marosy B, Marshall J, Martin R, Marvin C, Mawhinney M, McGee S, McGoldrick D, Mehaffey M, Mekonnen B, Meng X, Mitani T, Miyake C, Mohr D, Morris S, Mullen T, Murdock D, Murugan M, Muzny D, Myers B, Neira J, Nguyen K, Nielsen P, Nudelman N, O’Heir E, O’Leary M, Ongaco C, Orange J, Osei-Owusu I, Paine I, Pais L, Paschall J, Patterson K, Pehlivan D, Pelle B, Penney S, Chavez J, Pierce-Hoffman E, Poli C, Punetha J, Radhakrishnan A, Richardson M, Rodrigues E, Roote G, Rosenfeld J, Ryke E, Sabo A, Sanchez A, Schrauwen I, Scott D, Sedlazeck F, Serrano J, Shaw C, Shelford T, Shively K, Singer-Berk M, Smith J, Snow H, Snyder G, Solomonson M, Son R, Song X, Stankiewicz P, Stephan T, Sutton V, Sveden A, Sánchez D, Tackett M, Talkowski M, Threlkeld M, Tiao G, Udler M, Vail L, Valivullah Z, Valkanas E, VanNoy G, Wang Q, Wang G, Wang L, Wangler M, Watts N, Weisburd B, Weiss J, Wheeler M, White J, Williamson C, Wilson M, Wiszniewski W, Withers M, Witmer D, Witzgall L, Wohler E, Wojcik M, Wong I, Wood J, Wu N, Xing J, Yang Y, Yi Q, Yuan B, Zeiger J, Zhang C, Zhang P, Zhang Y, Zhang X, Zhang Y, Zhang S, Zoghbi H, van den Veyver I, Rehm H, O’Donnell-Luria A. Centers for Mendelian Genomics: A decade of facilitating gene discovery. Genetics In Medicine 2022, 24: 784-797. PMID: 35148959, PMCID: PMC9119004, DOI: 10.1016/j.gim.2021.12.005.Peer-Reviewed Original ResearchConceptsGene discoveryMendelian GenomicsUnderstanding of genesGene-phenotype relationshipsGenome variationWorldwide data sharingCandidate genesMendelian phenotypesGenomic researchGenome sequencingMatchmaker ExchangeGenomicsGenesSequencingBiomedical researchMajor roleDiscoveryExomePhenotypeRoleGenotypesCommunityImplications of Selection Bias Due to Delayed Study Entry in Clinical Genomic Studies
Brown S, Lavery J, Shen R, Martin A, Kehl K, Sweeney S, Lepisto E, Rizvi H, McCarthy C, Schultz N, Warner J, Park B, Bedard P, Riely G, Schrag D, Panageas K, Sweeney S, Foti M, Khotskaya Y, Fiandalo M, Gross B, Schultz N, Mastrogiacomo B, Sarmardy M, Li M, Resnick A, Waanders A, Lilly J, Carvajal R, Rabadan R, Ingham M, Hsaio S, Abraham J, Brenton J, Rueda O, Caldas C, Valgañón M, Silva D, Boursnell C, Garcia R, Rodriguez E, Nimmervoll B, Cerami E, Ducar M, Kumari P, Lindeman N, MacConnaill L, Orechia J, Schrag D, Shivdasani P, Van Allen E, Johnson J, Jänne P, Lepisto E, Hassett M, Pimentel S, Sripakdeevong P, Janeway K, Johnson J, Meyerson M, Quinn D, Cushing O, Haigis K, Miller D, Kehl K, Gustav A, Tramontano A, Baquero S, Bell J, Green M, McCall S, Datto M, Calvo F, Andre F, Guillaume M, Dogan S, Ludovic L, Scoazec J, Ardenos M, Vassal G, Michels S, Velculescu V, Baras A, Gocke C, Brahmer J, Sawyers C, Solit D, Gardos S, Berger M, Ladanyi M, Riely G, Sirintrapun J, Panageas K, Caroline A, Thomas S, Zarski A, Zehir A, Iasonosa A, Philip J, Brown S, Kung A, Kundra R, Rudolph J, Lavery J, Rivzi H, Schwartz J, McCarthy C, Bhuiya M, Martin A, Chu C, DuBois R, van de Velde T, Meijer G, Horlings H, van Tinteren H, Lolkema M, Nijman L, Bierkens M, Hoeve J, Voest E, Hiemstra A, Sonke G, Craenmehr J, Hudecek J, Monkhorst K, Urba W, Bernard B, Piening B, Bifulco C, Tittel P, Cramer J, Guinney J, Yu T, Guo X, Acebedo A, Gold P, Bailey N, Kadri S, Segal J, Pankhuri W, Wang P, George S, Christine M, Van't Veer L, Talevich E, Wren A, Sweet-Cordero A, Turski M, Bedard P, KamelReid S, Lu Z, Pugh T, Siu L, Watt S, Leighl N, Yu C, Ahmed L, Krishna G, Virtaenen C, Chow H, Plagianakos D, Del Rossi S, Singaravelan N, Hakgor S, Qazi N, Nguyen A, Stickle N, Stricker T, Micheel C, Anderson I, Jones L, Wang L, Lovly C, LeNoue Newton M, Park B, Warner J, Fabbri D, Coco J, Ye C, Chaugai S, Mishra S, Yang Y, Wen L, Dienstmann R, Aguilar Izquierdo S, Viaplana Donato C, Mancuso F, Topaloglu U, Liu L, Guan M, Zhang W, Jin G, Knight J, D'Eletto M, Ormay E, Mane S, Bilguvar K, Zenta W, Dykas D. Implications of Selection Bias Due to Delayed Study Entry in Clinical Genomic Studies. JAMA Oncology 2022, 8: 287-291. PMID: 34734967, PMCID: PMC9190030, DOI: 10.1001/jamaoncol.2021.5153.Peer-Reviewed Original ResearchConceptsOverall survivalStage IV non-small cell lung cancerNon-small cell lung cancerStage IV colorectal cancerUnadjusted median survivalCell lung cancerMedian survivalStudy entryCancer outcomesColorectal cancerLung cancerMolecular testingSurvival analysisGeneralizable research findingsClinical genomic studiesSurvivalCancerSelection biasAppropriate statistical methodsDiagnosisAmerican Association
2021
Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non–Small Cell Lung or Colorectal Cancer
Kehl K, Riely G, Lepisto E, Lavery J, Warner J, LeNoue-Newton M, Sweeney S, Rudolph J, Brown S, Yu C, Bedard P, Schrag D, Panageas K, Sweeney S, Foti M, Khotskaya Y, Fiandalo M, Gross B, Schultz N, Mastrogiacomo B, Sarmardy M, Li M, Resnick A, Waanders A, Lilly J, Carvajal R, Rabadan R, Ingham M, Hsaio S, Abraham J, Brenton J, Rueda O, Caldas C, Valgañón M, Silva D, Boursnell C, Garcia R, Rodriguez E, Nimmervoll B, Cerami E, Ducar M, Kumari P, Lindeman N, MacConnaill L, Orechia J, Schrag D, Shivdasani P, Van Allen E, Johnson J, Jänne P, Lepisto E, Hassett M, Pimentel S, Sripakdeevong P, Janeway K, Johnson J, Meyerson M, Quinn D, Cushing O, Haigis K, Miller D, Kehl K, Gustav A, Tramontano A, Baquero S, Bell J, Green M, McCall S, Datto M, Calvo F, Andre F, Guillaume M, Dogan S, Ludovic L, Scoazec J, Ardenos M, Vassal G, Michels S, Velculescu V, Baras A, Gocke C, Brahmer J, Sawyers C, Solit D, Gardos S, Berger M, Ladanyi M, Riely G, Sirintrapun J, Caroline A, Thomas S, Zarski A, Zehir A, Iasonosa A, Philip J, Brown S, Kung A, Kundra R, Rudolph J, Lavery J, Rivzi H, Schwartz J, McCarthy C, Bhuiya M, Martin A, Chu C, DuBois R, van de Velde T, Meijer G, Horlings H, van Tinteren H, Lolkema M, Nijman L, Bierkens M, Hoeve J, Voest E, Hiemstra A, Sonke G, Craenmehr J, Hudecek J, Monkhorst K, Urba W, Bernard B, Piening B, Bifulco C, Tittel P, Cramer J, Guinney J, Yu T, Guo X, Acebedo A, Gold P, Bailey N, Kadri S, Segal J, Pankhuri W, Wang P, George S, Christine M, Van't Veer L, Talevich E, Wren A, Sweet-Cordero A, Turski M, Bedard P, KamelReid S, Lu Z, Pugh T, Siu L, Watt S, Leighl N, Yu C, Ahmed L, Krishna G, Virtaenen C, Chow H, Plagianakos D, Del Rossi S, Singaravelan N, Hakgor S, Qazi N, Nguyen A, Stickle N, Stricker T, Micheel C, Anderson I, Jones L, Wang L, Lovly C, LeNoue Newton M, Park B, Warner J, Fabbri D, Coco J, Ye C, Chaugai S, Mishra S, Yang Y, Wen L, Dienstmann R, Aguilar Izquierdo S, Viaplana Donato C, Mancuso F, Topaloglu U, Liu L, Guan M, Zhang W, Jin G, Knight J, D'Eletto M, Ormay E, Mane S, Bilguvar K, Zenta W, Dykas D. Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non–Small Cell Lung or Colorectal Cancer. JAMA Network Open 2021, 4: e2117547. PMID: 34309669, PMCID: PMC8314138, DOI: 10.1001/jamanetworkopen.2021.17547.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCandidate surrogate end pointsProgression-free survivalSurrogate end pointsOverall survivalTreatment discontinuationColorectal cancerEnd pointCohort studyNext treatmentNon-small cell lungRetrospective cohort studyAlternative end pointsCell lung cancerKey end pointsAdvanced diseasePrimary outcomeSystemic therapyCell lungLung cancerProlonged survivalMAIN OUTCOMEProgression eventsAcademic centersPatients
2020
Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
Jin SC, Lewis SA, Bakhtiari S, Zeng X, Sierant MC, Shetty S, Nordlie SM, Elie A, Corbett MA, Norton BY, van Eyk CL, Haider S, Guida BS, Magee H, Liu J, Pastore S, Vincent JB, Brunstrom-Hernandez J, Papavasileiou A, Fahey MC, Berry JG, Harper K, Zhou C, Zhang J, Li B, Zhao H, Heim J, Webber DL, Frank MSB, Xia L, Xu Y, Zhu D, Zhang B, Sheth AH, Knight JR, Castaldi C, Tikhonova IR, López-Giráldez F, Keren B, Whalen S, Buratti J, Doummar D, Cho M, Retterer K, Millan F, Wang Y, Waugh JL, Rodan L, Cohen JS, Fatemi A, Lin AE, Phillips JP, Feyma T, MacLennan SC, Vaughan S, Crompton KE, Reid SM, Reddihough DS, Shang Q, Gao C, Novak I, Badawi N, Wilson YA, McIntyre SJ, Mane SM, Wang X, Amor DJ, Zarnescu DC, Lu Q, Xing Q, Zhu C, Bilguvar K, Padilla-Lopez S, Lifton RP, Gecz J, MacLennan AH, Kruer MC. Mutations disrupting neuritogenesis genes confer risk for cerebral palsy. Nature Genetics 2020, 52: 1046-1056. PMID: 32989326, PMCID: PMC9148538, DOI: 10.1038/s41588-020-0695-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCerebral PalsyCyclin DCytoskeletonDrosophilaExomeExome SequencingExtracellular MatrixF-Box ProteinsFemaleFocal AdhesionsGenetic Predisposition to DiseaseGenome, HumanHumansMaleMutationNeuritesRhoB GTP-Binding ProteinRisk FactorsSequence Analysis, DNASignal TransductionTubulinTumor Suppressor ProteinsConceptsDamaging de novo mutationsCerebral palsyDe novo mutationsCerebral palsy casesRisk genesDamaging de novoNovo mutationsWhole-exome sequencingPalsy casesNeuromotor functionD levelsMonogenic etiologyCyclin D levelsNeuronal connectivityPalsyGene confer riskConfer riskRecessive variantsNeurodevelopmental disorder genesReverse genetic screenDisorder genesParent-offspring triosGenome-wide significanceGenomic factorsCytoskeleton pathwayAutoantibodies against type I IFNs in patients with life-threatening COVID-19
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Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020, 370: eabd4585. PMID: 32972996, PMCID: PMC7857397, DOI: 10.1126/science.abd4585.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionType I IFNI IFNAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionLife-threatening COVID-19 pneumoniaMild SARS-CoV-2 infectionSyndrome coronavirus 2 infectionCoronavirus disease 2019 (COVID-19) pneumoniaLife-threatening COVID-19Coronavirus 2 infectionCOVID-19 pneumoniaImmunoglobulin G autoantibodiesType I IFNsTypes of IFNI IFNsHealthy individualsClinical variabilityPatientsInborn errorsIFNCritical diseaseInfectionAutoantibodiesPneumoniaInborn errors of type I IFN immunity in patients with life-threatening COVID-19
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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
2019
Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis
Timberlake AT, Jin SC, Nelson-Williams C, Wu R, Furey CG, Islam B, Haider S, Loring E, Galm A, Steinbacher D, Larysz D, Staffenberg D, Flores R, Rodriguez E, Boggon T, Persing J, Lifton R, Lifton RP, Gunel M, Mane S, Bilguvar K, Gerstein M, Loring E, Nelson-Williams C, Lopez F, Knight J. Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 15116-15121. PMID: 31292255, PMCID: PMC6660739, DOI: 10.1073/pnas.1902041116.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlpha CateninChildChild, PreschoolCraniosynostosesExomeExome SequencingFemaleGene ExpressionGlypicansHistone AcetyltransferasesHumansMaleMutationNuclear ProteinsPedigreeRisk AssessmentSignal TransductionSkullSOXC Transcription FactorsTranscription Factor AP-2Zinc Finger Protein Gli2ConceptsRare damaging mutationsSyndromic craniosynostosisCongenital anomaliesDamaging mutationsSyndromic casesExome sequencingAdditional congenital anomaliesFrequent congenital anomaliesDamaging de novo mutationsNeural crest cell migrationDamaging de novoCrest cell migrationCS patientsMutation burdenChromatin modifiersSubsequent childrenTranscription factorsDe novo mutationsCS casesCS geneHedgehog pathwayDisease locusPremature fusionFunction mutationsCraniosynostosis
2018
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation
Duran D, Zeng X, Jin SC, Choi J, Nelson-Williams C, Yatsula B, Gaillard J, Furey CG, Lu Q, Timberlake AT, Dong W, Sorscher MA, Loring E, Klein J, Allocco A, Hunt A, Conine S, Karimy JK, Youngblood MW, Zhang J, DiLuna ML, Matouk CC, Mane S, Tikhonova IR, Castaldi C, López-Giráldez F, Knight J, Haider S, Soban M, Alper SL, Komiyama M, Ducruet AF, Zabramski JM, Dardik A, Walcott BP, Stapleton CJ, Aagaard-Kienitz B, Rodesch G, Jackson E, Smith ER, Orbach DB, Berenstein A, Bilguvar K, Vikkula M, Gunel M, Lifton RP, Kahle KT. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron 2018, 101: 429-443.e4. PMID: 30578106, PMCID: PMC10292091, DOI: 10.1016/j.neuron.2018.11.041.Peer-Reviewed Original ResearchConceptsChromatin modifiersVascular developmentSpecification of arteriesDeep venous systemNormal vascular developmentParent-offspring triosSignaling GenesGalen malformationDamaging mutationsGenesMutationsEssential roleArterio-venous malformationsCutaneous vascular abnormalitiesNovo mutationsExome sequencingDisease biologyIncomplete penetranceVariable expressivityVascular abnormalitiesVenous systemMutation carriersArterial bloodMutation burdenClinical implicationsLoss 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 expressionBiallelic 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
2017
Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands
Jin SC, Homsy J, Zaidi S, Lu Q, Morton S, DePalma SR, Zeng X, Qi H, Chang W, Sierant MC, Hung WC, Haider S, Zhang J, Knight J, Bjornson RD, Castaldi C, Tikhonoa IR, Bilguvar K, Mane SM, Sanders SJ, Mital S, Russell MW, Gaynor JW, Deanfield J, Giardini A, Porter GA, Srivastava D, Lo CW, Shen Y, Watkins WS, Yandell M, Yost HJ, Tristani-Firouzi M, Newburger JW, Roberts AE, Kim R, Zhao H, Kaltman JR, Goldmuntz E, Chung WK, Seidman JG, Gelb BD, Seidman CE, Lifton RP, Brueckner M. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nature Genetics 2017, 49: 1593-1601. PMID: 28991257, PMCID: PMC5675000, DOI: 10.1038/ng.3970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutistic DisorderCardiac MyosinsCase-Control StudiesChildExomeFemaleGene ExpressionGenetic Predisposition to DiseaseGenome-Wide Association StudyGrowth Differentiation Factor 1Heart Defects, CongenitalHeterozygoteHigh-Throughput Nucleotide SequencingHomozygoteHumansMaleMutationMyosin Heavy ChainsPedigreeRiskVascular Endothelial Growth Factor Receptor-3