Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
Jin SC, Dong W, Kundishora AJ, Panchagnula S, Moreno-De-Luca A, Furey CG, Allocco AA, Walker RL, Nelson-Williams C, Smith H, Dunbar A, Conine S, Lu Q, Zeng X, Sierant MC, Knight JR, Sullivan W, Duy PQ, DeSpenza T, Reeves BC, Karimy JK, Marlier A, Castaldi C, Tikhonova IR, Li B, Peña HP, Broach JR, Kabachelor EM, Ssenyonga P, Hehnly C, Ge L, Keren B, Timberlake AT, Goto J, Mangano FT, Johnston JM, Butler WE, Warf BC, Smith ER, Schiff SJ, Limbrick DD, Heuer G, Jackson EM, Iskandar BJ, Mane S, Haider S, Guclu B, Bayri Y, Sahin Y, Duncan CC, Apuzzo MLJ, DiLuna ML, Hoffman EJ, Sestan N, Ment LR, Alper SL, Bilguvar K, Geschwind DH, Günel M, Lifton RP, Kahle KT. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus. Nature Medicine 2020, 26: 1754-1765. PMID: 33077954, PMCID: PMC7871900, DOI: 10.1038/s41591-020-1090-2.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusPoor neurodevelopmental outcomesPost-surgical patientsCerebrospinal fluid accumulationNeural stem cell biologyGenetic disruptionWhole-exome sequencingPrimary pathomechanismEarly brain developmentNeurodevelopmental outcomesHigh morbidityCSF diversionMutation burdenFluid accumulationBrain ventriclesCH casesBrain developmentDe novo mutationsPatientsExome sequencingCSF dynamicsDisease mechanismsHydrocephalusNovo mutationsCell typesInflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets
Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD, Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT. Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nature Reviews Neurology 2020, 16: 285-296. PMID: 32152460, PMCID: PMC7375440, DOI: 10.1038/s41582-020-0321-y.Peer-Reviewed Original ResearchConceptsPosthaemorrhagic hydrocephalusPostinfectious hydrocephalusNeurosurgical disordersPathogenic mechanismsToll-like receptor 4Pathogenesis of hydrocephalusImportant protective responseEpendymal denudationCommon neurosurgical disorderSustained inflammationInflammatory mediatorsNeuroinflammatory conditionsImmune cellsReceptor 4Therapeutic approachesReparative inflammationCerebrospinal fluidCSF pathwaysHydrocephalusTherapeutic targetInflammationTherapeutic interventionsBrain ventriclesProtective responsePhysical irritants