0000000000381006

AUTHOR

Małgorzata J.m. Nowaczyk

showing 3 related works from this author

Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants

2019

Purpose: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. Methods: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. Results: The number of rare likely deleterious variants in functionally intolerant genes (“other hits”) correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with thei…

MaleParents0301 basic medicineProbandNeuronalGenetic Carrier Screening16p11.2 deletion030105 genetics & heredityCognitionFamily historyNeural Cell Adhesion MoleculesGenetics (clinical)Exome sequencingSequence DeletionGeneticsGenetic Carrier ScreeningPhenotypePenetrancePedigreePhenotypeAutistic Disorder/genetics; Autistic Disorder/physiopathology; Cell Adhesion Molecules Neuronal/genetics; Chromosomes Human Pair 16/genetics; Cognition/physiology; DNA Copy Number Variations/genetics; Female; Gene Expression Regulation/genetics; Genetic Background; Genetic Carrier Screening; Humans; Male; Methyltransferases/genetics; Nerve Tissue Proteins/genetics; Parents; Pedigree; Phenotype; Proteins/genetics; Sequence Deletion/genetics; Siblings; 16p11.2 deletion; CNV; autism; modifier; phenotypic variabilityFemaleGenetic BackgroundHumanDNA Copy Number VariationsCell Adhesion Molecules NeuronalCNVautismNerve Tissue ProteinsBiologyChromosomesArticle03 medical and health sciencesmental disordersmedicineHumansAutistic DisorderBiologyGenemodifierPair 16SiblingsCalcium-Binding ProteinsProteinsMethyltransferasesmedicine.disease16p11.2 deletion; autism; CNV; modifier; phenotypic variability; Genetics (clinical)Cytoskeletal Proteins030104 developmental biologyGene Expression Regulation[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human geneticsAutismphenotypic variabilityHuman medicine16p11.2 deletion; autism; CNV; modifier; phenotypic variability; Autistic Disorder; Cell Adhesion Molecules Neuronal; Chromosomes Human Pair 16; Cognition; DNA Copy Number Variations; Female; Gene Expression Regulation; Genetic Background; Humans; Male; Methyltransferases; Nerve Tissue Proteins; Parents; Pedigree; Phenotype; Proteins; Sequence Deletion; Siblings; Genetic Carrier ScreeningCell Adhesion MoleculesChromosomes Human Pair 16Transcription FactorsGenetics in Medicine
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Baraitser-Winter cerebrofrontofacial syndrome : Delineation of the spectrum in 42 cases

2015

International audience; Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode beta- and gamma-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris…

MaleMicrocephalyPathologyCraniofacial abnormality[SDV]Life Sciences [q-bio]MedizinGYRAL MALFORMATIONSCraniofacial AbnormalitiesFUNCTIONAL DIVERSITY0302 clinical medicinePtosisGene OrderGenetics(clinical)HypertelorismNon-U.S. Gov'tChildGenetics (clinical)ArthrogryposisDystonia0303 health sciencesResearch Support Non-U.S. Gov'tAnatomy3. Good healthPhenotypeChild PreschoolFemalemedicine.symptomAbnormalitiesMultipleRare cancers Radboud Institute for Health Sciences [Radboudumc 9]Adultmedicine.medical_specialtyAPPARENTLY UNDESCRIBED SYNDROMEAdolescentLissencephalyBiologyResearch SupportArticle03 medical and health sciencesYoung AdultSDG 3 - Good Health and Well-beingmedicineGeneticsJournal ArticleHumansAbnormalities MultiplePreschool030304 developmental biologySHALLOW ORBITSNeurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]GAMMA-ACTINPachygyriaFaciesmedicine.diseaseIRIS COLOBOMAActinsBETA-ACTINAbnormalities Multiple; Actins; Adolescent; Adult; Amino Acid Substitution; Child; Child Preschool; Craniofacial Abnormalities; Facies; Female; Gene Order; Genetic Loci; Humans; Male; Mutation; Phenotype; Young AdultAmino Acid SubstitutionGenetic LociFACIAL SYNDROMEMutation030217 neurology & neurosurgeryMENTAL-RETARDATIONGROWTH-RETARDATION
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Rare variants in the genetic background modulate the expressivity of neurodevelopmental disorders

2018

AbstractPurposeTo assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations.MethodsWe analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated mutations.ResultsThe number of rare secondary mutations in functionally intolerant genes (second-hits) correlated with the expressivity of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in probands with autism carrying gene-disruptive mutations (n=184, p=0.03) compared to …

GeneticsProband0303 health sciencesCandidate geneMutationGenetic heterogeneityDiseaseBiologymedicine.diseasemedicine.disease_cause03 medical and health sciences0302 clinical medicinemedicineAutismExpressivity (genetics)Family history030217 neurology & neurosurgery030304 developmental biology
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