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 microcephalyRecessive COL4A2 Mutation Leads to Intellectual Disability, Epilepsy, and Spastic Cerebral Palsy
Bakhtiari S, Tafakhori A, Jin SC, Guida BS, Alehabib E, Firouzbadi S, Bilguvar K, Fahey MC, Darvish H, Kruer MC. Recessive COL4A2 Mutation Leads to Intellectual Disability, Epilepsy, and Spastic Cerebral Palsy. Neurology Genetics 2021, 7: e583. PMID: 33912663, PMCID: PMC8077768, DOI: 10.1212/nxg.0000000000000583.Peer-Reviewed Original ResearchCerebral palsySpastic cerebral palsyCortical visual impairmentBasement membrane thickeningStroke-related complicationsWhite matter diseaseIntellectual disabilityEarly fetal developmentCerebral calcificationsHemorrhagic strokeAutosomal dominant fashionMembrane thickeningPostnatal periodFunction effectsCOL4A2 mutationsFetal developmentClinical diagnosisVisual impairmentPalsyEpilepsyDiseaseDominant fashionGenes COL4A1Muscular systemDisability