7 recherche sur le mot-clé 'DNA Copy Number Variations'

Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder / Chia-Lin YIN in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 23p. Titre : Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder Type de document : texte imprimé Auteurs : Chia-Lin YIN, Auteur ; Hsin-I CHEN, Auteur ; Ling-Hui LI, Auteur ; Yi-Ling CHIEN, Auteur ; Hsiao-Mei LIAO, Auteur ; Miao-Churn CHOU, Auteur ; Wen-Jiun CHOU, Auteur ; Wen-Che TSAI, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Chen-Zen LO, Auteur ; Jer-Yuarn WU, Auteur ; Yen-Tsz CHEN, Auteur ; Susan Shur-Fen GAU, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Adolescent  Asian Continental Ancestry Group/genetics  Autism Spectrum Disorder/etiology/genetics  Child  China  Cohort Studies  DNA Copy Number Variations  Down-Regulation  Exons  Female  Genome-Wide Association Study  Genotype  Humans  Male  Odds Ratio  Pedigree  Phenotype  Polymorphism, Single Nucleotide  Ubiquitin-Protein Ligases/genetics  Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Family study  Gene expression  Park2 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754. En ligne : http://dx.doi.org/10.1186/s13229-016-0087-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder [texte imprimé] / Chia-Lin YIN, Auteur ; Hsin-I CHEN, Auteur ; Ling-Hui LI, Auteur ; Yi-Ling CHIEN, Auteur ; Hsiao-Mei LIAO, Auteur ; Miao-Churn CHOU, Auteur ; Wen-Jiun CHOU, Auteur ; Wen-Che TSAI, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Chen-Zen LO, Auteur ; Jer-Yuarn WU, Auteur ; Yen-Tsz CHEN, Auteur ; Susan Shur-Fen GAU, Auteur . - 23p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 23p. Mots-clés : Adolescent  Asian Continental Ancestry Group/genetics  Autism Spectrum Disorder/etiology/genetics  Child  China  Cohort Studies  DNA Copy Number Variations  Down-Regulation  Exons  Female  Genome-Wide Association Study  Genotype  Humans  Male  Odds Ratio  Pedigree  Phenotype  Polymorphism, Single Nucleotide  Ubiquitin-Protein Ligases/genetics  Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Family study  Gene expression  Park2 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754. En ligne : http://dx.doi.org/10.1186/s13229-016-0087-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Genetic Testing in Patients with Neurodevelopmental Disorders: Experience of 511 Patients at Cincinnati Children's Hospital Medical Center / Xiaoli DU in Journal of Autism and Developmental Disorders, 52-11 (November 2022)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 52-11 (November 2022) . - p.4828-4842 Titre : Genetic Testing in Patients with Neurodevelopmental Disorders: Experience of 511 Patients at Cincinnati Children's Hospital Medical Center Type de document : texte imprimé Auteurs : Xiaoli DU, Auteur ; Jennifer Elaine GLASS, Auteur ; Stephanie BALOW, Auteur ; Lisa M. DYER, Auteur ; Pamela A. RATHBUN, Auteur ; Qiaoning GUAN, Auteur ; Jie LIU, Auteur ; Yaning WU, Auteur ; D. Brian DAWSON, Auteur ; Lauren WALTERS-SEN, Auteur ; Teresa A. SMOLAREK, Auteur ; Wenying ZHANG, Auteur Article en page(s) : p.4828-4842 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis  Child  DNA Copy Number Variations  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/diagnosis/genetics  Genetic Testing  Hospitals  Humans  Male  Mutation  Neurodevelopmental Disorders/diagnosis/genetics  Retrospective Studies  Trinucleotide Repeat Expansion  Autism spectrum disorder (ASD)  Copy number variant (CNV)  Fragile X  Mecp2  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : Our institution developed and continuously improved a Neurodevelopmental Reflex (NDR) algorithm to help physicians with genetic test ordering for neurodevelopmental disorders (NDDs). To assess its performance, we performed a retrospective study of 511 patients tested through NDR from 2018 to 2019. SNP Microarray identified pathogenic/likely pathogenic copy number variations in 27/511 cases (5.28%). Among the 484 patients tested for Fragile X FMR1 CGG repeats, a diagnosis (0.20%) was established for one male mosaic for a full mutation, a premutation, and a one-CGG allele. Within the 101 normocephalic female patients tested for MECP2, two patients were found to carry pathogenic variants (1.98%). This retrospective study suggested the NDR algorithm effectively established diagnoses for patients with NDDs with a yield of 5.87%. En ligne : http://dx.doi.org/10.1007/s10803-021-05337-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=489 [article] Genetic Testing in Patients with Neurodevelopmental Disorders: Experience of 511 Patients at Cincinnati Children's Hospital Medical Center [texte imprimé] / Xiaoli DU, Auteur ; Jennifer Elaine GLASS, Auteur ; Stephanie BALOW, Auteur ; Lisa M. DYER, Auteur ; Pamela A. RATHBUN, Auteur ; Qiaoning GUAN, Auteur ; Jie LIU, Auteur ; Yaning WU, Auteur ; D. Brian DAWSON, Auteur ; Lauren WALTERS-SEN, Auteur ; Teresa A. SMOLAREK, Auteur ; Wenying ZHANG, Auteur . - p.4828-4842. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 52-11 (November 2022) . - p.4828-4842 Mots-clés : Autism Spectrum Disorder/diagnosis  Child  DNA Copy Number Variations  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/diagnosis/genetics  Genetic Testing  Hospitals  Humans  Male  Mutation  Neurodevelopmental Disorders/diagnosis/genetics  Retrospective Studies  Trinucleotide Repeat Expansion  Autism spectrum disorder (ASD)  Copy number variant (CNV)  Fragile X  Mecp2  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : Our institution developed and continuously improved a Neurodevelopmental Reflex (NDR) algorithm to help physicians with genetic test ordering for neurodevelopmental disorders (NDDs). To assess its performance, we performed a retrospective study of 511 patients tested through NDR from 2018 to 2019. SNP Microarray identified pathogenic/likely pathogenic copy number variations in 27/511 cases (5.28%). Among the 484 patients tested for Fragile X FMR1 CGG repeats, a diagnosis (0.20%) was established for one male mosaic for a full mutation, a premutation, and a one-CGG allele. Within the 101 normocephalic female patients tested for MECP2, two patients were found to carry pathogenic variants (1.98%). This retrospective study suggested the NDR algorithm effectively established diagnoses for patients with NDDs with a yield of 5.87%. En ligne : http://dx.doi.org/10.1007/s10803-021-05337-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=489

Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech / Marion LESIEUR-SEBELLIN ; Karine SIQUIER-PERNET ; Geoffroy DELPLANCQ ; Marlene RIO ; Mélanie PARISOT ; Patrick NITSCHKÉ ; Cristina RODRIGUEZ-FONTENLA ; Alison BODINEAU ; Lucie NARCY ; Emilie SCHLUMBERGER ; Vincent CANTAGREL ; Valérie MALAN in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 10 p. Titre : Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech Type de document : texte imprimé Auteurs : Marion LESIEUR-SEBELLIN, Auteur ; Karine SIQUIER-PERNET, Auteur ; Geoffroy DELPLANCQ, Auteur ; Marlene RIO, Auteur ; Mélanie PARISOT, Auteur ; Patrick NITSCHKÉ, Auteur ; Cristina RODRIGUEZ-FONTENLA, Auteur ; Alison BODINEAU, Auteur ; Lucie NARCY, Auteur ; Emilie SCHLUMBERGER, Auteur ; Vincent CANTAGREL, Auteur ; Valérie MALAN, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Child  Language Development Disorders/genetics  Apraxias/genetics  Child, Preschool  Intellectual Disability/genetics  DNA Copy Number Variations  Adolescent  Genetic Predisposition to Disease  15q13.3 locus  16p11.2 locus  Autism  Developmental language disorder  Intellectual disability  Neurodevelopmental disorders  ZNF292  use the data for research and publication purposes. Competing interests: The  authors declare no competing interests. Ethics approval and consent to  participate: Written informed consent was obtained from all individuals. All  studies were carried out in accordance with the declaration of Helsinki and were  approved by a national ethics committee (CPP Ile de France, RIPH2G reference DI  24.01180.000212, N°2024-A00519-38, CPP reference 29-2024, promoter reference  C23-79  promoter: Inserm). ClinicalTrials.gov Identifier: NCT06660108. Index. décimale : PER Périodiques Résumé : BACKGROUND: Developmental language disorder (DLD) refers to children who present with language difficulties that are not due to a known biomedical condition or associated with autism spectrum disorder (ASD) or intellectual disability (ID). The clinical heterogeneity of language disorders, the frequent presence of comorbidities, and the inconsistent terminology used over the years have impeded both research and clinical practice. Identifying sub-groups of children (i.e. DLD cases without childhood apraxia of speech (CAS)) with language difficulties is essential for elucidating the underlying genetic causes of this condition. DLD presents along a spectrum of severity, ranging from mild speech delays to profound disturbances in oral language structure in otherwise typically intelligent children. The prevalence of DLD is ~ 7-8% or 2% if severe forms are considered. This study aims to investigate a homogeneous cohort of DLD patients, excluding cases of ASD, ID or CAS, using multiple genomic approaches to better define the molecular basis of the disorder. METHODS: Fifteen families, including 27 children with severe DLD, were enrolled. The majority of cases (n = 24) were included in multiplex families while three cases were sporadic. This resulted in a cohort of 59 individuals for whom chromosomal microarray analysis and exome or genome sequencing were performed. RESULTS: We identified copy number variants (CNVs) predisposing to neurodevelopmental disorders with incomplete penetrance and variable expressivity in two families. These CNVs (i.e., 15q13.3 deletion and proximal 16p11.2 duplication) are interpreted as pathogenic. In one sporadic case, a de novo pathogenic variant in the ZNF292 gene, known to be associated with ID, was detected, broadening the spectrum of this syndrome. LIMITATIONS: The strict diagnostic criteria applied by our multidisciplinary team, including speech-language physicians, neuropsychologists, and paediatric neurologists, resulted in a relatively small sample size, which limit the strength of our findings. CONCLUSION: These findings highlight a common genetic architecture between DLD, ASD and ID, and underline the need for further investigation into overlapping neurodevelopmental pathways. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06660108. En ligne : https://dx.doi.org/10.1186/s13229-025-00642-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech [texte imprimé] / Marion LESIEUR-SEBELLIN, Auteur ; Karine SIQUIER-PERNET, Auteur ; Geoffroy DELPLANCQ, Auteur ; Marlene RIO, Auteur ; Mélanie PARISOT, Auteur ; Patrick NITSCHKÉ, Auteur ; Cristina RODRIGUEZ-FONTENLA, Auteur ; Alison BODINEAU, Auteur ; Lucie NARCY, Auteur ; Emilie SCHLUMBERGER, Auteur ; Vincent CANTAGREL, Auteur ; Valérie MALAN, Auteur . - 10 p. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 10 p. Mots-clés : Humans  Male  Female  Child  Language Development Disorders/genetics  Apraxias/genetics  Child, Preschool  Intellectual Disability/genetics  DNA Copy Number Variations  Adolescent  Genetic Predisposition to Disease  15q13.3 locus  16p11.2 locus  Autism  Developmental language disorder  Intellectual disability  Neurodevelopmental disorders  ZNF292  use the data for research and publication purposes. Competing interests: The  authors declare no competing interests. Ethics approval and consent to  participate: Written informed consent was obtained from all individuals. All  studies were carried out in accordance with the declaration of Helsinki and were  approved by a national ethics committee (CPP Ile de France, RIPH2G reference DI  24.01180.000212, N°2024-A00519-38, CPP reference 29-2024, promoter reference  C23-79  promoter: Inserm). ClinicalTrials.gov Identifier: NCT06660108. Index. décimale : PER Périodiques Résumé : BACKGROUND: Developmental language disorder (DLD) refers to children who present with language difficulties that are not due to a known biomedical condition or associated with autism spectrum disorder (ASD) or intellectual disability (ID). The clinical heterogeneity of language disorders, the frequent presence of comorbidities, and the inconsistent terminology used over the years have impeded both research and clinical practice. Identifying sub-groups of children (i.e. DLD cases without childhood apraxia of speech (CAS)) with language difficulties is essential for elucidating the underlying genetic causes of this condition. DLD presents along a spectrum of severity, ranging from mild speech delays to profound disturbances in oral language structure in otherwise typically intelligent children. The prevalence of DLD is ~ 7-8% or 2% if severe forms are considered. This study aims to investigate a homogeneous cohort of DLD patients, excluding cases of ASD, ID or CAS, using multiple genomic approaches to better define the molecular basis of the disorder. METHODS: Fifteen families, including 27 children with severe DLD, were enrolled. The majority of cases (n = 24) were included in multiplex families while three cases were sporadic. This resulted in a cohort of 59 individuals for whom chromosomal microarray analysis and exome or genome sequencing were performed. RESULTS: We identified copy number variants (CNVs) predisposing to neurodevelopmental disorders with incomplete penetrance and variable expressivity in two families. These CNVs (i.e., 15q13.3 deletion and proximal 16p11.2 duplication) are interpreted as pathogenic. In one sporadic case, a de novo pathogenic variant in the ZNF292 gene, known to be associated with ID, was detected, broadening the spectrum of this syndrome. LIMITATIONS: The strict diagnostic criteria applied by our multidisciplinary team, including speech-language physicians, neuropsychologists, and paediatric neurologists, resulted in a relatively small sample size, which limit the strength of our findings. CONCLUSION: These findings highlight a common genetic architecture between DLD, ASD and ID, and underline the need for further investigation into overlapping neurodevelopmental pathways. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06660108. En ligne : https://dx.doi.org/10.1186/s13229-025-00642-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude / Jocelyn J. LEBLANC in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 30p. Titre : Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude Type de document : texte imprimé Auteurs : Jocelyn J. LEBLANC, Auteur ; Charles A. NELSON, Auteur Article en page(s) : 30p. Langues : Anglais (eng) Mots-clés : Adolescent  Child  Child, Preschool  Chromosomes, Human, Pair 16/genetics  DNA Copy Number Variations  Developmental Disabilities/diagnosis/physiopathology  Electroencephalography  Evoked Potentials, Visual/physiology  Female  Gene Deletion  Gene Duplication  Humans  Male  Visual Cortex/diagnostic imaging  16p11.2 copy number variation  Visual cortex  Visual evoked potential Index. décimale : PER Périodiques Résumé : BACKGROUND: Duplication and deletion of the chromosomal region 16p11.2 cause a broad range of impairments, including intellectual disability, language disorders, and sensory symptoms. However, it is unclear how changes in 16p11.2 dosage affect cortical circuitry during development. The aim of this study was to investigate whether the visual evoked potential (VEP) could be used as a noninvasive quantitative measure of cortical processing in children with 16p11.2 copy number variation. METHODS: Pattern-reversal VEPs were successfully recorded in 19 deletion carriers, 9 duplication carriers, and 13 typically developing children between the ages of 3 and 14 years. The stimulus was a black and white checkerboard (60') that reversed contrast at 2 Hz. VEP responses were extracted from continuous EEG recorded using a high-density elasticized electrode net. RESULTS: Quantitative analysis of the VEP waveform revealed that, relative to controls, deletion carriers displayed increased amplitude and duplication carriers displayed diminished amplitude. Latencies of the VEP waveform components were unaffected by 16p11.2 status. P1 amplitude did not correlate with age, IQ, or head circumference. CONCLUSIONS: The results of this study suggest that recording VEP is a useful method to assay cortical processing in children with 16p11.2 copy number variation. There is a gene dosage-dependent effect on P1 amplitude that merits further investigation. The VEP is directly translatable to animal models, offering a promising way to probe the neurobiological mechanisms underlying cortical dysfunction in this developmental disorder. En ligne : http://dx.doi.org/10.1186/s13229-016-0095-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude [texte imprimé] / Jocelyn J. LEBLANC, Auteur ; Charles A. NELSON, Auteur . - 30p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 30p. Mots-clés : Adolescent  Child  Child, Preschool  Chromosomes, Human, Pair 16/genetics  DNA Copy Number Variations  Developmental Disabilities/diagnosis/physiopathology  Electroencephalography  Evoked Potentials, Visual/physiology  Female  Gene Deletion  Gene Duplication  Humans  Male  Visual Cortex/diagnostic imaging  16p11.2 copy number variation  Visual cortex  Visual evoked potential Index. décimale : PER Périodiques Résumé : BACKGROUND: Duplication and deletion of the chromosomal region 16p11.2 cause a broad range of impairments, including intellectual disability, language disorders, and sensory symptoms. However, it is unclear how changes in 16p11.2 dosage affect cortical circuitry during development. The aim of this study was to investigate whether the visual evoked potential (VEP) could be used as a noninvasive quantitative measure of cortical processing in children with 16p11.2 copy number variation. METHODS: Pattern-reversal VEPs were successfully recorded in 19 deletion carriers, 9 duplication carriers, and 13 typically developing children between the ages of 3 and 14 years. The stimulus was a black and white checkerboard (60') that reversed contrast at 2 Hz. VEP responses were extracted from continuous EEG recorded using a high-density elasticized electrode net. RESULTS: Quantitative analysis of the VEP waveform revealed that, relative to controls, deletion carriers displayed increased amplitude and duplication carriers displayed diminished amplitude. Latencies of the VEP waveform components were unaffected by 16p11.2 status. P1 amplitude did not correlate with age, IQ, or head circumference. CONCLUSIONS: The results of this study suggest that recording VEP is a useful method to assay cortical processing in children with 16p11.2 copy number variation. There is a gene dosage-dependent effect on P1 amplitude that merits further investigation. The VEP is directly translatable to animal models, offering a promising way to probe the neurobiological mechanisms underlying cortical dysfunction in this developmental disorder. En ligne : http://dx.doi.org/10.1186/s13229-016-0095-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome / Kathleen E. WILSON in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome Type de document : texte imprimé Auteurs : Kathleen E. WILSON, Auteur ; Ari M. FISH, Auteur ; Catherine MANKIW, Auteur ; Anastasia XENOPHONTOS, Auteur ; Allysa WARLING, Auteur ; Ethan WHITMAN, Auteur ; Liv CLASEN, Auteur ; Erin TORRES, Auteur ; Jonathan BLUMENTHAL, Auteur ; Armin RAZNAHAN, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder  Child  Child, Preschool  DNA Copy Number Variations  Family  Humans  Male  Sex Chromosome Disorders  XYY Karyotype  Young Adult  Copy number variants  Modeling penetrance  Neurogenetic disorders  Precision psychiatry  Sex chromosome aneuploidies  Health (NIMH). The authors have no additional competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome-a sex chromosome aneuploidy that is known to increase risk for psychopathology. METHODS: We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits. RESULTS: Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R(2) ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring. CONCLUSIONS: We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggest that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." Date of registry: 01 October 1989. En ligne : https://dx.doi.org/10.1186/s11689-021-09360-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome [texte imprimé] / Kathleen E. WILSON, Auteur ; Ari M. FISH, Auteur ; Catherine MANKIW, Auteur ; Anastasia XENOPHONTOS, Auteur ; Allysa WARLING, Auteur ; Ethan WHITMAN, Auteur ; Liv CLASEN, Auteur ; Erin TORRES, Auteur ; Jonathan BLUMENTHAL, Auteur ; Armin RAZNAHAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder  Child  Child, Preschool  DNA Copy Number Variations  Family  Humans  Male  Sex Chromosome Disorders  XYY Karyotype  Young Adult  Copy number variants  Modeling penetrance  Neurogenetic disorders  Precision psychiatry  Sex chromosome aneuploidies  Health (NIMH). The authors have no additional competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome-a sex chromosome aneuploidy that is known to increase risk for psychopathology. METHODS: We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits. RESULTS: Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R(2) ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring. CONCLUSIONS: We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggest that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." Date of registry: 01 October 1989. En ligne : https://dx.doi.org/10.1186/s11689-021-09360-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder / Jordi PIJUAN in Autism Research, 14-6 (June 2021)  

Permalink

Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings / Kei OHASHI in Journal of Autism and Developmental Disorders, 51-12 (December 2021)  

Permalink