Clinicopathological Stratification of Idiopathic Autism and Autism with 15q11.2–q13 Duplications / Jerzy WEGIEL

Public ISBD in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Titre : Clinicopathological Stratification of Idiopathic Autism and Autism with 15q11.2–q13 Duplications Type de document : Texte imprimé et/ou numérique Auteurs : Jerzy WEGIEL, Auteur ; N. Carolyn SCHANEN, Auteur ; Edwin H. Jr COOK, Auteur ; W. Ted BROWN, Auteur ; Izabela KUCHNA, Auteur ; Krzysztof NOWICKI, Auteur ; Jarek WEGIEL, Auteur ; Humi IMAKI, Auteur ; Shuang Yong MA, Auteur ; Eric LONDON, Auteur ; Thomas WISNIEWSKI, Auteur Année de publication : 2013 Importance : p.347-359 Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Postmortem studies of brains of individuals with idiopathic autism and 15q11.2–q13 duplications autism (dup(15)) identify a cluster of neuropathological features differentiating these cohorts. They show a need for both reclassification of autism according to etiology, clinical presentation and neuropathology, and a commonality of clinical and neuropathological traits justifying autism diagnosis. The features differentiating these cohorts include: (a) maternal origin in patients with dup(15); (b) autism in 78% of subjects; (c) more severe clinical phenotypes, with intellectual deficit (100%), early-onset of severe or intractable seizures in 78% of subjects, and increased prevalence (up to 67%) of sudden unexplained death; (d) high prevalence of microcephaly, with mean brain weight 300g less than in idiopathic autism; (e) several-fold increase in the number of developmental abnormalities, including defects of migration and dysplastic changes, especially numerous in the hippocampal formation; and (f) significant increase in the intraneuronal amyloid load, reflecting enhanced amyloid-? precursor protein processing with ?-secretase. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189 in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Clinicopathological Stratification of Idiopathic Autism and Autism with 15q11.2–q13 Duplications [Texte imprimé et/ou numérique] / Jerzy WEGIEL, Auteur ; N. Carolyn SCHANEN, Auteur ; Edwin H. Jr COOK, Auteur ; W. Ted BROWN, Auteur ; Izabela KUCHNA, Auteur ; Krzysztof NOWICKI, Auteur ; Jarek WEGIEL, Auteur ; Humi IMAKI, Auteur ; Shuang Yong MA, Auteur ; Eric LONDON, Auteur ; Thomas WISNIEWSKI, Auteur . - 2013 . - p.347-359. Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Postmortem studies of brains of individuals with idiopathic autism and 15q11.2–q13 duplications autism (dup(15)) identify a cluster of neuropathological features differentiating these cohorts. They show a need for both reclassification of autism according to etiology, clinical presentation and neuropathology, and a commonality of clinical and neuropathological traits justifying autism diagnosis. The features differentiating these cohorts include: (a) maternal origin in patients with dup(15); (b) autism in 78% of subjects; (c) more severe clinical phenotypes, with intellectual deficit (100%), early-onset of severe or intractable seizures in 78% of subjects, and increased prevalence (up to 67%) of sudden unexplained death; (d) high prevalence of microcephaly, with mean brain weight 300g less than in idiopathic autism; (e) several-fold increase in the number of developmental abnormalities, including defects of migration and dysplastic changes, especially numerous in the hippocampal formation; and (f) significant increase in the intraneuronal amyloid load, reflecting enhanced amyloid-? precursor protein processing with ?-secretase. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189

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The Interstitial Duplication 15q11.2-q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature / Nora URRACA in Autism Research, 6-4 (August 2013)  

Public ISBD [article]  inAutism Research > 6-4 (August 2013) . - p.268-279 Titre : The Interstitial Duplication 15q11.2-q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature Type de document : Texte imprimé et/ou numérique Auteurs : Nora URRACA, Auteur ; Julie CLEARY, Auteur ; Victoria BREWER, Auteur ; Eniko K. PIVNICK, Auteur ; Kathryn MCVICAR, Auteur ; Ronald L. THIBERT, Auteur ; N. Carolyn SCHANEN, Auteur ; Carmen ESMER, Auteur ; Dustin LAMPORT, Auteur ; Lawrence T. REITER, Auteur Article en page(s) : p.268-279 Langues : Anglais (eng) Mots-clés : autism  15q duplication  imprinting  copy number variation  UBE3A Index. décimale : PER Périodiques Résumé : Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. En ligne : http://dx.doi.org/10.1002/aur.1284 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=212 [article] The Interstitial Duplication 15q11.2-q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature [Texte imprimé et/ou numérique] / Nora URRACA, Auteur ; Julie CLEARY, Auteur ; Victoria BREWER, Auteur ; Eniko K. PIVNICK, Auteur ; Kathryn MCVICAR, Auteur ; Ronald L. THIBERT, Auteur ; N. Carolyn SCHANEN, Auteur ; Carmen ESMER, Auteur ; Dustin LAMPORT, Auteur ; Lawrence T. REITER, Auteur . - p.268-279. Langues : Anglais (eng) in Autism Research > 6-4 (August 2013) . - p.268-279 Mots-clés : autism  15q duplication  imprinting  copy number variation  UBE3A Index. décimale : PER Périodiques Résumé : Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. En ligne : http://dx.doi.org/10.1002/aur.1284 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=212

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