Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism / H. G. KIM in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 35 p. Titre : Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism Type de document : Texte imprimé et/ou numérique Auteurs : H. G. KIM, Auteur ; J. A. ROSENFELD, Auteur ; D. A. SCOTT, Auteur ; G. BENEDICTE, Auteur ; J. D. LABONNE, Auteur ; J. BROWN, Auteur ; M. MCGUIRE, Auteur ; S. MAHIDA, Auteur ; S. NAIDU, Auteur ; J. GUTIERREZ, Auteur ; G. LESCA, Auteur ; V. DES PORTES, Auteur ; A. L. BRUEL, Auteur ; A. SORLIN, Auteur ; F. XIA, Auteur ; Y. CAPRI, Auteur ; E. MULLER, Auteur ; D. MCKNIGHT, Auteur ; E. TORTI, Auteur ; F. RUSCHENDORF, Auteur ; O. HUMMEL, Auteur ; Z. ISLAM, Auteur ; P. R. KOLATKAR, Auteur ; L. C. LAYMAN, Auteur ; D. RYU, Auteur ; I. K. KONG, Auteur ; S. MADAN-KHETARPAL, Auteur ; C. H. KIM, Auteur Article en page(s) : 35 p. Langues : Anglais (eng) Mots-clés : AT Hook domain  Autism spectrum disorder (ASD)  Bhc80  Intellectual disability (ID)  Intrinsically disordered region (IDR)  Kdm1a  Neurodevelopmental disorders  Phf21a  Potocki-Shaffer syndrome (PSS) Index. décimale : PER Périodiques Résumé : Background: PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. Methods: Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. Results: We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. Conclusion: Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype. En ligne : https://dx.doi.org/10.1186/s13229-019-0286-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism [Texte imprimé et/ou numérique] / H. G. KIM, Auteur ; J. A. ROSENFELD, Auteur ; D. A. SCOTT, Auteur ; G. BENEDICTE, Auteur ; J. D. LABONNE, Auteur ; J. BROWN, Auteur ; M. MCGUIRE, Auteur ; S. MAHIDA, Auteur ; S. NAIDU, Auteur ; J. GUTIERREZ, Auteur ; G. LESCA, Auteur ; V. DES PORTES, Auteur ; A. L. BRUEL, Auteur ; A. SORLIN, Auteur ; F. XIA, Auteur ; Y. CAPRI, Auteur ; E. MULLER, Auteur ; D. MCKNIGHT, Auteur ; E. TORTI, Auteur ; F. RUSCHENDORF, Auteur ; O. HUMMEL, Auteur ; Z. ISLAM, Auteur ; P. R. KOLATKAR, Auteur ; L. C. LAYMAN, Auteur ; D. RYU, Auteur ; I. K. KONG, Auteur ; S. MADAN-KHETARPAL, Auteur ; C. H. KIM, Auteur . - 35 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 35 p. Mots-clés : AT Hook domain  Autism spectrum disorder (ASD)  Bhc80  Intellectual disability (ID)  Intrinsically disordered region (IDR)  Kdm1a  Neurodevelopmental disorders  Phf21a  Potocki-Shaffer syndrome (PSS) Index. décimale : PER Périodiques Résumé : Background: PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. Methods: Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. Results: We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. Conclusion: Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype. En ligne : https://dx.doi.org/10.1186/s13229-019-0286-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Erratum to: The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications / M. A. GILLENTINE in Journal of Autism and Developmental Disorders, 47-3 (March 2017)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 47-3 (March 2017) . - p.563-563 Titre : Erratum to: The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications Type de document : Texte imprimé et/ou numérique Auteurs : M. A. GILLENTINE, Auteur ; Leandra N. BERRY, Auteur ; R. P. GOIN-KOCHEL, Auteur ; M. A. ALI, Auteur ; J. GE, Auteur ; D. GUFFEY, Auteur ; J. A. ROSENFELD, Auteur ; V. HANNIG, Auteur ; P. BADER, Auteur ; M. PROUD, Auteur ; M. SHINAWI, Auteur ; B. H. GRAHAM, Auteur ; A. LIN, Auteur ; S. R. LALANI, Auteur ; J. REYNOLDS, Auteur ; M. CHEN, Auteur ; T. GREBE, Auteur ; C. G. MINARD, Auteur ; P. STANKIEWICZ, Auteur ; Arthur L. BEAUDET, Auteur ; Christian P. SCHAAF, Auteur Article en page(s) : p.563-563 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1007/s10803-017-3047-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304 [article] Erratum to: The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications [Texte imprimé et/ou numérique] / M. A. GILLENTINE, Auteur ; Leandra N. BERRY, Auteur ; R. P. GOIN-KOCHEL, Auteur ; M. A. ALI, Auteur ; J. GE, Auteur ; D. GUFFEY, Auteur ; J. A. ROSENFELD, Auteur ; V. HANNIG, Auteur ; P. BADER, Auteur ; M. PROUD, Auteur ; M. SHINAWI, Auteur ; B. H. GRAHAM, Auteur ; A. LIN, Auteur ; S. R. LALANI, Auteur ; J. REYNOLDS, Auteur ; M. CHEN, Auteur ; T. GREBE, Auteur ; C. G. MINARD, Auteur ; P. STANKIEWICZ, Auteur ; Arthur L. BEAUDET, Auteur ; Christian P. SCHAAF, Auteur . - p.563-563. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 47-3 (March 2017) . - p.563-563 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1007/s10803-017-3047-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304

De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures / B. ROYER-BERTRAND in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 69 p. Titre : De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures Type de document : Texte imprimé et/ou numérique Auteurs : B. ROYER-BERTRAND, Auteur ; M. JEQUIER GYGAX, Auteur ; K. CISAROVA, Auteur ; J. A. ROSENFELD, Auteur ; J. A. BASSETTI, Auteur ; O. MOLDOVAN, Auteur ; E. O'HEIR, Auteur ; L. C. BURRAGE, Auteur ; J. ALLEN, Auteur ; L. T. EMRICK, Auteur ; E. EASTMAN, Auteur ; C. KUMPS, Auteur ; S. ABBAS, Auteur ; G. VAN WINCKEL, Auteur ; Nadia CHABANE, Auteur ; E. H. ZACKAI, Auteur ; S. LEBON, Auteur ; B. KEENA, Auteur ; E. J. BHOJ, Auteur ; M. UMAIR, Auteur ; D. LI, Auteur ; K. A. DONALD, Auteur ; A. SUPERTI-FURGA, Auteur Article en page(s) : 69 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Cacna1e  Developmental regression  Epilepsy  Exome sequencing  Global developmental delay  Intellectual disability  Neurodevelopmental disorders  Seizures  Topiramate  receives revenue from clinical genetic testing completed at Baylor Genetics  Laboratories. Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo variants in the voltage-gated calcium channel subunit ?1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. METHODS: Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. RESULTS: We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype-phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. LIMITATIONS: The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. CONCLUSIONS: Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate. En ligne : http://dx.doi.org/10.1186/s13229-021-00473-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures [Texte imprimé et/ou numérique] / B. ROYER-BERTRAND, Auteur ; M. JEQUIER GYGAX, Auteur ; K. CISAROVA, Auteur ; J. A. ROSENFELD, Auteur ; J. A. BASSETTI, Auteur ; O. MOLDOVAN, Auteur ; E. O'HEIR, Auteur ; L. C. BURRAGE, Auteur ; J. ALLEN, Auteur ; L. T. EMRICK, Auteur ; E. EASTMAN, Auteur ; C. KUMPS, Auteur ; S. ABBAS, Auteur ; G. VAN WINCKEL, Auteur ; Nadia CHABANE, Auteur ; E. H. ZACKAI, Auteur ; S. LEBON, Auteur ; B. KEENA, Auteur ; E. J. BHOJ, Auteur ; M. UMAIR, Auteur ; D. LI, Auteur ; K. A. DONALD, Auteur ; A. SUPERTI-FURGA, Auteur . - 69 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 69 p. Mots-clés : Autism spectrum disorder  Cacna1e  Developmental regression  Epilepsy  Exome sequencing  Global developmental delay  Intellectual disability  Neurodevelopmental disorders  Seizures  Topiramate  receives revenue from clinical genetic testing completed at Baylor Genetics  Laboratories. Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo variants in the voltage-gated calcium channel subunit ?1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. METHODS: Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. RESULTS: We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype-phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. LIMITATIONS: The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. CONCLUSIONS: Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate. En ligne : http://dx.doi.org/10.1186/s13229-021-00473-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications / J. A. ROSENFELD in Journal of Neurodevelopmental Disorders, 2-1 (March 2010)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 2-1 (March 2010) . - p.26-38 Titre : Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications Type de document : Texte imprimé et/ou numérique Auteurs : J. A. ROSENFELD, Auteur ; J. COPPINGER, Auteur ; B. A. BEJJANI, Auteur ; S. GIRIRAJAN, Auteur ; E. E. EICHLER, Auteur ; L. G. SHAFFER, Auteur ; B. C. BALLIF, Auteur Article en page(s) : p.26-38 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Microdeletions and microduplications encompassing a ~593-kb region of 16p11.2 have been implicated as one of the most common genetic causes of susceptibility to autism/autism spectrum disorder (ASD). We report 45 microdeletions and 32 microduplications of 16p11.2, representing 0.78% of 9,773 individuals referred to our laboratory for microarray-based comparative genomic hybridization (aCGH) testing for neurodevelopmental and congenital anomalies. The microdeletion was de novo in 17 individuals and maternally inherited in five individuals for whom parental testing was available. Detailed histories of 18 individuals with 16p11.2 microdeletions were reviewed; all had developmental delays with below-average intelligence, and a majority had speech or language problems or delays and various behavioral problems. Of the 16 individuals old enough to be evaluated for autism, the speech/behavior profiles of seven did not suggest the need for ASD evaluation. Of the remaining nine individuals who had speech/behavior profiles that aroused clinical suspicion of ASD, five had formal evaluations, and three had PDD-NOS. Of the 19 microduplications with parental testing, five were de novo, nine were maternally inherited, and five were paternally inherited. A majority with the microduplication had delayed development and/or specific deficits in speech or language, though these features were not as consistent as seen with the microdeletions. This study, which is the largest cohort of individuals with 16p11.2 alterations reported to date, suggests that 16p11.2 microdeletions and microduplications are associated with a high frequency of cognitive, developmental, and speech delay and behavior abnormalities. Furthermore, although features associated with these alterations can be found in individuals with ASD, additional factors are likely required to lead to the development of ASD. En ligne : http://dx.doi.org/10.1007/s11689-009-9037-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342 [article] Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications [Texte imprimé et/ou numérique] / J. A. ROSENFELD, Auteur ; J. COPPINGER, Auteur ; B. A. BEJJANI, Auteur ; S. GIRIRAJAN, Auteur ; E. E. EICHLER, Auteur ; L. G. SHAFFER, Auteur ; B. C. BALLIF, Auteur . - p.26-38. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 2-1 (March 2010) . - p.26-38 Index. décimale : PER Périodiques Résumé : Microdeletions and microduplications encompassing a ~593-kb region of 16p11.2 have been implicated as one of the most common genetic causes of susceptibility to autism/autism spectrum disorder (ASD). We report 45 microdeletions and 32 microduplications of 16p11.2, representing 0.78% of 9,773 individuals referred to our laboratory for microarray-based comparative genomic hybridization (aCGH) testing for neurodevelopmental and congenital anomalies. The microdeletion was de novo in 17 individuals and maternally inherited in five individuals for whom parental testing was available. Detailed histories of 18 individuals with 16p11.2 microdeletions were reviewed; all had developmental delays with below-average intelligence, and a majority had speech or language problems or delays and various behavioral problems. Of the 16 individuals old enough to be evaluated for autism, the speech/behavior profiles of seven did not suggest the need for ASD evaluation. Of the remaining nine individuals who had speech/behavior profiles that aroused clinical suspicion of ASD, five had formal evaluations, and three had PDD-NOS. Of the 19 microduplications with parental testing, five were de novo, nine were maternally inherited, and five were paternally inherited. A majority with the microduplication had delayed development and/or specific deficits in speech or language, though these features were not as consistent as seen with the microdeletions. This study, which is the largest cohort of individuals with 16p11.2 alterations reported to date, suggests that 16p11.2 microdeletions and microduplications are associated with a high frequency of cognitive, developmental, and speech delay and behavior abnormalities. Furthermore, although features associated with these alterations can be found in individuals with ASD, additional factors are likely required to lead to the development of ASD. En ligne : http://dx.doi.org/10.1007/s11689-009-9037-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342

The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications / M. A. GILLENTINE in Journal of Autism and Developmental Disorders, 47-3 (March 2017)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 47-3 (March 2017) . - p.549-562 Titre : The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications Type de document : Texte imprimé et/ou numérique Auteurs : M. A. GILLENTINE, Auteur ; Leandra N. BERRY, Auteur ; R. P. GOIN-KOCHEL, Auteur ; M. A. ALI, Auteur ; J. GE, Auteur ; D. GUFFEY, Auteur ; J. A. ROSENFELD, Auteur ; V. HANNIG, Auteur ; P. BADER, Auteur ; M. PROUD, Auteur ; M. SHINAWI, Auteur ; B. H. GRAHAM, Auteur ; A. LIN, Auteur ; S. R. LALANI, Auteur ; J. REYNOLDS, Auteur ; M. CHEN, Auteur ; T. GREBE, Auteur ; C. G. MINARD, Auteur ; P. STANKIEWICZ, Auteur ; Arthur L. BEAUDET, Auteur ; Christian P. SCHAAF, Auteur Article en page(s) : p.549-562 Langues : Anglais (eng) Mots-clés : 15q13.3 microduplication  CHRNA7  Neurodevelopment  Behavior  Autism spectrum disorder Index. décimale : PER Périodiques Résumé : Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals. En ligne : http://dx.doi.org/10.1007/s10803-016-2961-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304 [article] The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications [Texte imprimé et/ou numérique] / M. A. GILLENTINE, Auteur ; Leandra N. BERRY, Auteur ; R. P. GOIN-KOCHEL, Auteur ; M. A. ALI, Auteur ; J. GE, Auteur ; D. GUFFEY, Auteur ; J. A. ROSENFELD, Auteur ; V. HANNIG, Auteur ; P. BADER, Auteur ; M. PROUD, Auteur ; M. SHINAWI, Auteur ; B. H. GRAHAM, Auteur ; A. LIN, Auteur ; S. R. LALANI, Auteur ; J. REYNOLDS, Auteur ; M. CHEN, Auteur ; T. GREBE, Auteur ; C. G. MINARD, Auteur ; P. STANKIEWICZ, Auteur ; Arthur L. BEAUDET, Auteur ; Christian P. SCHAAF, Auteur . - p.549-562. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 47-3 (March 2017) . - p.549-562 Mots-clés : 15q13.3 microduplication  CHRNA7  Neurodevelopment  Behavior  Autism spectrum disorder Index. décimale : PER Périodiques Résumé : Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals. En ligne : http://dx.doi.org/10.1007/s10803-016-2961-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304

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