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Sensory processing in 16p11.2 deletion and 16p11.2 duplication / Harriet SMITH in Autism Research, 15-11 (November 2022)
[article]
Titre : Sensory processing in 16p11.2 deletion and 16p11.2 duplication Type de document : Texte imprimé et/ou numérique Auteurs : Harriet SMITH, Auteur ; Chloe LANE, Auteur ; Reem AL-JAWAHIRI, Auteur ; Megan FREETH, Auteur Article en page(s) : p.2081-2098 Langues : Anglais (eng) Mots-clés : Child Humans Chromosome Deletion Autism Spectrum Disorder/genetics Autistic Disorder/genetics Intellectual Disability/genetics Perception Chromosomes, Human, Pair 16/genetics Chromosome Disorders/complications/genetics Adhd anxiety autistic sensory processing sensory systems Index. décimale : PER Périodiques Résumé : Deletions and duplications at the chromosomal region of 16p11.2 have a broad range of phenotypic effects including increased likelihood of intellectual disability, autism, attention deficit hyperactivity disorder (ADHD), epilepsy, and language and motor delays. However, whether and how sensory processing is affected has not yet been considered in detail. Parents/caregivers of 38 children with a 16p11.2 deletion and 31 children with a 16p11.2 duplication completed the Sensory Behavior Questionnaire (SBQ) and the Child Sensory Profile 2 (CSP-2) along with other standardized questionnaires assessing autistic traits (SRS-2), ADHD traits (Conners 3), anxiety (SCAS-P) and adaptive behavior (VABS-3). SBQ and CSP-2 responses found that sensory processing differences were clearly evident in both 16p11.2 deletion and 16p11.2 duplication, though there was significant variation in both cohorts. SBQ data indicated the frequency and impact of sensory behavior were more severe when compared to neurotypical children, with levels being similar to autistic children. CSP-2 data indicated over 70% of children displayed clear differences in sensory registration (missing sensory input). Seventy-one percent with 16p11.2 duplications were also unusually sensitive to sensory information and 57% with 16p11.2 duplications were unusually avoidant of sensory stimuli. This first detailed assessment of sensory processing, alongside other clinical features, in relatively large cohorts of children with a 16p11.2 deletion and 16p11.2 duplication demonstrates that sensory processing differences have a profound impact on their lives. En ligne : http://dx.doi.org/10.1002/aur.2802 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488
in Autism Research > 15-11 (November 2022) . - p.2081-2098[article] Sensory processing in 16p11.2 deletion and 16p11.2 duplication [Texte imprimé et/ou numérique] / Harriet SMITH, Auteur ; Chloe LANE, Auteur ; Reem AL-JAWAHIRI, Auteur ; Megan FREETH, Auteur . - p.2081-2098.
Langues : Anglais (eng)
in Autism Research > 15-11 (November 2022) . - p.2081-2098
Mots-clés : Child Humans Chromosome Deletion Autism Spectrum Disorder/genetics Autistic Disorder/genetics Intellectual Disability/genetics Perception Chromosomes, Human, Pair 16/genetics Chromosome Disorders/complications/genetics Adhd anxiety autistic sensory processing sensory systems Index. décimale : PER Périodiques Résumé : Deletions and duplications at the chromosomal region of 16p11.2 have a broad range of phenotypic effects including increased likelihood of intellectual disability, autism, attention deficit hyperactivity disorder (ADHD), epilepsy, and language and motor delays. However, whether and how sensory processing is affected has not yet been considered in detail. Parents/caregivers of 38 children with a 16p11.2 deletion and 31 children with a 16p11.2 duplication completed the Sensory Behavior Questionnaire (SBQ) and the Child Sensory Profile 2 (CSP-2) along with other standardized questionnaires assessing autistic traits (SRS-2), ADHD traits (Conners 3), anxiety (SCAS-P) and adaptive behavior (VABS-3). SBQ and CSP-2 responses found that sensory processing differences were clearly evident in both 16p11.2 deletion and 16p11.2 duplication, though there was significant variation in both cohorts. SBQ data indicated the frequency and impact of sensory behavior were more severe when compared to neurotypical children, with levels being similar to autistic children. CSP-2 data indicated over 70% of children displayed clear differences in sensory registration (missing sensory input). Seventy-one percent with 16p11.2 duplications were also unusually sensitive to sensory information and 57% with 16p11.2 duplications were unusually avoidant of sensory stimuli. This first detailed assessment of sensory processing, alongside other clinical features, in relatively large cohorts of children with a 16p11.2 deletion and 16p11.2 duplication demonstrates that sensory processing differences have a profound impact on their lives. En ligne : http://dx.doi.org/10.1002/aur.2802 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488 Psychotic symptoms in 16p11.2 copy-number variant carriers / Amandeep JUTLA in Autism Research, 13-2 (February 2020)
[article]
Titre : Psychotic symptoms in 16p11.2 copy-number variant carriers Type de document : Texte imprimé et/ou numérique Auteurs : Amandeep JUTLA, Auteur ; J. Blake TURNER, Auteur ; LeeAnne GREEN SNYDER, Auteur ; Wendy K. CHUNG, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur Article en page(s) : p.187-198 Langues : Anglais (eng) Mots-clés : autism spectrum disorder chromosome deletion chromosome duplication chromosomes human obsessive-compulsive disorder pair 16 phenotype schizophrenia spectrum and other psychotic disorders Index. décimale : PER Périodiques Résumé : 16p11.2 copy-number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate, and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers. Autism Res 2020, 13: 187-198. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Either deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia (SCZ). In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of SCZ. En ligne : http://dx.doi.org/10.1002/aur.2232 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420
in Autism Research > 13-2 (February 2020) . - p.187-198[article] Psychotic symptoms in 16p11.2 copy-number variant carriers [Texte imprimé et/ou numérique] / Amandeep JUTLA, Auteur ; J. Blake TURNER, Auteur ; LeeAnne GREEN SNYDER, Auteur ; Wendy K. CHUNG, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur . - p.187-198.
Langues : Anglais (eng)
in Autism Research > 13-2 (February 2020) . - p.187-198
Mots-clés : autism spectrum disorder chromosome deletion chromosome duplication chromosomes human obsessive-compulsive disorder pair 16 phenotype schizophrenia spectrum and other psychotic disorders Index. décimale : PER Périodiques Résumé : 16p11.2 copy-number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate, and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers. Autism Res 2020, 13: 187-198. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Either deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia (SCZ). In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of SCZ. En ligne : http://dx.doi.org/10.1002/aur.2232 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420 Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome / A. KOLEVZON in Molecular Autism, 13 (2022)
[article]
Titre : Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. KOLEVZON, Auteur ; M. S. BREEN, Auteur ; P. M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Y. FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; M. P. TRELLES, Auteur ; B. LERMAN, Auteur ; R. RAPAPORT, Auteur ; J. D. BUXBAUM, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Child Chromosome Deletion Chromosome Disorders/drug therapy/genetics Chromosomes, Human, Pair 22 Humans Insulin-Like Growth Factor I/therapeutic use Pilot Projects Asd Autism spectrum disorder Igf-1 Insulin-like growth factor-1 Pms Phelan-McDermid syndrome shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Molecular Autism > 13 (2022) . - 17 p.[article] Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / A. KOLEVZON, Auteur ; M. S. BREEN, Auteur ; P. M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Y. FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; M. P. TRELLES, Auteur ; B. LERMAN, Auteur ; R. RAPAPORT, Auteur ; J. D. BUXBAUM, Auteur . - 17 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 17 p.
Mots-clés : Child Chromosome Deletion Chromosome Disorders/drug therapy/genetics Chromosomes, Human, Pair 22 Humans Insulin-Like Growth Factor I/therapeutic use Pilot Projects Asd Autism spectrum disorder Igf-1 Insulin-like growth factor-1 Pms Phelan-McDermid syndrome shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations / S. DE RUBEIS in Molecular Autism, 9 (2018)
[article]
Titre : Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations Type de document : Texte imprimé et/ou numérique Auteurs : S. DE RUBEIS, Auteur ; P. M. SIPER, Auteur ; A. DURKIN, Auteur ; J. WEISSMAN, Auteur ; F. MURATET, Auteur ; Danielle B. HALPERN, Auteur ; M. D. P. TRELLES, Auteur ; Y. FRANK, Auteur ; R. LOZANO, Auteur ; A. Ting WANG, Auteur ; J. L. HOLDER, Auteur ; Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Child Child, Preschool Chromosome Deletion Chromosome Disorders/genetics/pathology Chromosomes, Human, Pair 22/genetics Female Haploinsufficiency Humans Male Nerve Tissue Proteins/genetics Phenotype Point Mutation 22q13 deletion syndrome Autism spectrum disorder Intellectual disability Phelan-McDermid syndrome shank3 Sequence variants Index. décimale : PER Périodiques Résumé : Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to SHANK3 haploinsufficiency, but also usually encompassing many other genes. While the number of point mutations identified in SHANK3 has increased in recent years due to large-scale sequencing studies, systematic studies describing the phenotype of individuals harboring such mutations are lacking. Methods: We provide detailed clinical and genetic data on 17 individuals carrying mutations in SHANK3. We also review 60 previously reported patients with pathogenic or likely pathogenic SHANK3 variants, often lacking detailed phenotypic information. Results: SHANK3 mutations in our cohort and in previously reported cases were distributed throughout the protein; the majority were truncating and all were compatible with de novo inheritance. Despite substantial allelic heterogeneity, four variants were recurrent (p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A), suggesting that these are hotspots for de novo mutations. All individuals studied had intellectual disability, and autism spectrum disorder was prevalent (73%). Severe speech deficits were common, but in contrast to individuals with 22q13.3 deletions, the majority developed single words, including 41% with at least phrase speech. Other common findings were consistent with reports among individuals with 22q13.3 deletions, including hypotonia, motor skill deficits, regression, seizures, brain abnormalities, mild dysmorphic features, and feeding and gastrointestinal problems. Conclusions: Haploinsufficiency of SHANK3 resulting from point mutations is sufficient to cause a broad range of features associated with PMS. Our findings expand the molecular and phenotypic spectrum of PMS caused by SHANK3 point mutations and suggest that, in general, speech impairment and motor deficits are more severe in the case of deletions. In contrast, renal abnormalities associated with 22q13.3 deletions do not appear to be related to the loss of SHANK3. En ligne : https://dx.doi.org/10.1186/s13229-018-0205-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 31p.[article] Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations [Texte imprimé et/ou numérique] / S. DE RUBEIS, Auteur ; P. M. SIPER, Auteur ; A. DURKIN, Auteur ; J. WEISSMAN, Auteur ; F. MURATET, Auteur ; Danielle B. HALPERN, Auteur ; M. D. P. TRELLES, Auteur ; Y. FRANK, Auteur ; R. LOZANO, Auteur ; A. Ting WANG, Auteur ; J. L. HOLDER, Auteur ; Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur . - 31p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 31p.
Mots-clés : Adolescent Adult Child Child, Preschool Chromosome Deletion Chromosome Disorders/genetics/pathology Chromosomes, Human, Pair 22/genetics Female Haploinsufficiency Humans Male Nerve Tissue Proteins/genetics Phenotype Point Mutation 22q13 deletion syndrome Autism spectrum disorder Intellectual disability Phelan-McDermid syndrome shank3 Sequence variants Index. décimale : PER Périodiques Résumé : Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to SHANK3 haploinsufficiency, but also usually encompassing many other genes. While the number of point mutations identified in SHANK3 has increased in recent years due to large-scale sequencing studies, systematic studies describing the phenotype of individuals harboring such mutations are lacking. Methods: We provide detailed clinical and genetic data on 17 individuals carrying mutations in SHANK3. We also review 60 previously reported patients with pathogenic or likely pathogenic SHANK3 variants, often lacking detailed phenotypic information. Results: SHANK3 mutations in our cohort and in previously reported cases were distributed throughout the protein; the majority were truncating and all were compatible with de novo inheritance. Despite substantial allelic heterogeneity, four variants were recurrent (p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A), suggesting that these are hotspots for de novo mutations. All individuals studied had intellectual disability, and autism spectrum disorder was prevalent (73%). Severe speech deficits were common, but in contrast to individuals with 22q13.3 deletions, the majority developed single words, including 41% with at least phrase speech. Other common findings were consistent with reports among individuals with 22q13.3 deletions, including hypotonia, motor skill deficits, regression, seizures, brain abnormalities, mild dysmorphic features, and feeding and gastrointestinal problems. Conclusions: Haploinsufficiency of SHANK3 resulting from point mutations is sufficient to cause a broad range of features associated with PMS. Our findings expand the molecular and phenotypic spectrum of PMS caused by SHANK3 point mutations and suggest that, in general, speech impairment and motor deficits are more severe in the case of deletions. In contrast, renal abnormalities associated with 22q13.3 deletions do not appear to be related to the loss of SHANK3. En ligne : https://dx.doi.org/10.1186/s13229-018-0205-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371