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 pathwayExome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia
Dong W, Jin SC, Allocco A, Zeng X, Sheth AH, Panchagnula S, Castonguay A, Lorenzo LÉ, Islam B, Brindle G, Bachand K, Hu J, Sularz A, Gaillard J, Choi J, Dunbar A, Nelson-Williams C, Kiziltug E, Furey CG, Conine S, Duy PQ, Kundishora AJ, Loring E, Li B, Lu Q, Zhou G, Liu W, Li X, Sierant MC, Mane S, Castaldi C, López-Giráldez F, Knight JR, Sekula RF, Simard JM, Eskandar EN, Gottschalk C, Moliterno J, Günel M, Gerrard JL, Dib-Hajj S, Waxman SG, Barker FG, Alper SL, Chahine M, Haider S, De Koninck Y, Lifton RP, Kahle KT. Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia. IScience 2020, 23: 101552. PMID: 33083721, PMCID: PMC7554653, DOI: 10.1016/j.isci.2020.101552.Peer-Reviewed Original ResearchTrigeminal neuralgiaNeuronal ion transportImpairment of GABAVoltage-gated CaMechanical allodyniaTN pathogenesisPain syndromePain behaviorGABA signalingReceptor ClDisease pathogenesisTN casesFamilial clusteringExome sequencingGenetic factorsVariant burdenNeuralgiaRare damaging variantsPathogenesisGABAChannel CaDamaging variantsProbandsParent-offspring triosLarge-scale genomic studies
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 implications
2015
De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies
Homsy J, Zaidi S, Shen Y, Ware JS, Samocha KE, Karczewski KJ, DePalma SR, McKean D, Wakimoto H, Gorham J, Jin SC, Deanfield J, Giardini A, Porter GA, Kim R, Bilguvar K, López-Giráldez F, Tikhonova I, Mane S, Romano-Adesman A, Qi H, Vardarajan B, Ma L, Daly M, Roberts AE, Russell MW, Mital S, Newburger JW, Gaynor JW, Breitbart RE, Iossifov I, Ronemus M, Sanders SJ, Kaltman JR, Seidman JG, Brueckner M, Gelb BD, Goldmuntz E, Lifton RP, Seidman CE, Chung WK. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science 2015, 350: 1262-1266. PMID: 26785492, PMCID: PMC4890146, DOI: 10.1126/science.aac9396.Peer-Reviewed Original ResearchConceptsCongenital anomaliesNeurodevelopmental disabilitiesCongenital heart disease patientsDe novo mutationsExtracardiac congenital anomaliesImproved prognostic assessmentEarly therapeutic interventionHeart disease patientsCongenital heart diseaseNovo mutationsCHD patientsDisease patientsHeart diseasePrognostic assessmentCHD casesTherapeutic interventionsPatientsExome sequencingCHDParent-offspring triosMultiple mutationsGenetic contributionMutationsChromatin modificationsTranscriptional regulation