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 typesPaenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants
Paulson J, Williams B, Hehnly C, Mishra N, Sinnar S, Zhang L, Ssentongo P, Mbabazi-Kabachelor E, Wijetunge D, von Bredow B, Mulondo R, Kiwanuka J, Bajunirwe F, Bazira J, Bebell L, Burgoine K, Couto-Rodriguez M, Ericson J, Erickson T, Ferrari M, Gladstone M, Guo C, Haran M, Hornig M, Isaacs A, Kaaya B, Kangere S, Kulkarni A, Kumbakumba E, Li X, Limbrick D, Magombe J, Morton S, Mugamba J, Ng J, Olupot-Olupot P, Onen J, Peterson M, Roy F, Sheldon K, Townsend R, Weeks A, Whalen A, Quackenbush J, Ssenyonga P, Galperin M, Almeida M, Atkins H, Warf B, Lipkin W, Broach J, Schiff S. Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants. Science Translational Medicine 2020, 12 PMID: 32998967, PMCID: PMC7774825, DOI: 10.1126/scitranslmed.aba0565.Peer-Reviewed Original ResearchConceptsPostinfectious hydrocephalusCSF samplesPIH casesPotential causative organismsCerebrospinal fluid accumulationCytomegalovirus coinfectionUgandan infantsNeonatal sepsisSurgical palliationNeonatal infectionInfant casesOptimal treatmentInfant cohortCommon causeCausative organismPediatric hydrocephalusFluid accumulationHydrocephalusAnaerobic bacterial isolatesControl casesInfectionFacultative anaerobic bacterial isolatesInfantsParasitic DNADisease