2021
Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy
Calame DG, Bakhtiari S, Logan R, Coban-Akdemir Z, Du H, Mitani T, Fatih JM, Hunter JV, Herman I, Pehlivan D, Jhangiani SN, Person R, Schnur RE, Jin SC, Bilguvar K, Posey JE, Koh S, Firouzabadi SG, Alehabib E, Tafakhori A, Esmkhani S, Gibbs RA, Noureldeen MM, Zaki MS, Marafi D, Darvish H, Kruer MC, Lupski JR. Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy. Genetics In Medicine 2021, 23: 2455-2460. PMID: 34385670, PMCID: PMC8633036, DOI: 10.1038/s41436-021-01291-x.Peer-Reviewed Original ResearchConceptsSpastic cerebral palsyC-terminal nuclear localization signalNuclear localization signalCerebral palsyPremature termination codonFunction variantsHuman neurodevelopmental disordersLocalization signalSplicing regulatorsGenomics initiativesLast exonRegulator geneTermination codonDisease traitsMutant transcriptsDevelopmental delayMouse neurodevelopmentSevere neurodevelopmental disorderMendelian disordersFunction variant allelesNeurodevelopmental disordersMolecular analysisPathogenic variationProtein 1Variable microcephalyMutation in ZDHHC15 Leads to Hypotonic Cerebral Palsy, Autism, Epilepsy, and Intellectual Disability
Lewis SA, Bakhtiari S, Heim J, Cornejo P, Liu J, Huang A, Musmacker A, Jin SC, Bilguvar K, Padilla-Lopez SR, Kruer MC. Mutation in ZDHHC15 Leads to Hypotonic Cerebral Palsy, Autism, Epilepsy, and Intellectual Disability. Neurology Genetics 2021, 7: e602. PMID: 34345675, PMCID: PMC8323736, DOI: 10.1212/nxg.0000000000000602.Peer-Reviewed Original ResearchHypotonic cerebral palsyCerebral palsyIntellectual disabilityOvoid lesionsMotor dysfunctionRare causeCerebral volumeTall foreheadDental crowdingMuscle hypotoniaNeurodevelopmental disabilitiesArched palateAnimal modelsPalpebral fissuresMild brachycephalyFunction genotypeNeurodevelopmental disordersPatient variantsPalsyPatientsEpilepsyLocomotor defectsFunction mutationsCandidate variantsDisability
2017
GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy
Yoo Y, Jung J, Lee Y, Lee Y, Cho H, Na E, Hong J, Kim E, Lee JS, Lee JS, Hong C, Park S, Wie J, Miller K, Shur N, Clow C, Ebel RS, DeBrosse SD, Henderson LB, Willaert R, Castaldi C, Tikhonova I, Bilgüvar K, Mane S, Kim KJ, Hwang YS, Lee S, So I, Lim BC, Choi H, Seong JY, Shin YB, Jung H, Chae J, Choi M. GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy. Annals Of Neurology 2017, 82: 466-478. PMID: 28856709, DOI: 10.1002/ana.25032.Peer-Reviewed Original ResearchConceptsRett syndromeGenetic factorsAppropriate medical interventionΓ-aminobutyric acid signalingDistinct diagnostic criteriaDevastating neurodevelopmental disorderWhole-exome sequencingAnn NeurolClinical featuresEE patientsEpileptic encephalopathyDe novo variantsNovel genetic factorsDiagnostic criteriaAnimal modelsMedical interventionsAccurate diagnosisReceptor activityReceptor functionSpecific molecular mechanismsPatientsRTT-like patientsNeurodevelopmental disordersNovo variantsMECP2 mutations