[article]
| Titre : |
Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns |
| Type de document : |
texte imprimé |
| Auteurs : |
Hailey SILVER, Auteur ; Rori GREENBERG, Auteur ; Paige M. SIPER, Auteur ; Jessica ZWEIFACH, Auteur ; Renee SOUFER, Auteur ; Mustafa SAHIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Alexander KOLEVZON, Auteur ; Dorothy E. GRICE, Auteur ; Joseph D. BUXBAUM, Auteur ; Tess LEVY, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Humans Autism Spectrum Disorder/genetics/physiopathology Male Female Nerve Tissue Proteins/genetics Child Child, Preschool Chromosome Disorders/genetics/physiopathology Developmental Disabilities/genetics/physiopathology Adolescent Attention Deficit Disorder with Hyperactivity/genetics Intellectual Disability/genetics Chromosomes, Human, Pair 22/genetics Adult Cohort Studies Chromosome Deletion Autism spectrum disorder Developmental delay Intellectual and developmental disability Phenotype SHANK2 Medicine at Mount Sinai’s Institutional Review Board (IRB) approved the study. Caregivers or legal guardians of the participants provided informed consent, and assent was obtained when applicable. Consent for publication: Not applicable. Competing interests: A.K. receives research support from AMO Pharma and consults for Acadia, Alkermes, Neuren, and GW Pharma. He serves on Scientific Advisory Boards for Ovid Therapeutics, Jaguar Therapeutics, and Ritrova Therapeutics. P.M.S. and Mount Sinai licensed the SAND developed by P.M.S. to Stoelting, Co. J.D.B. holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary professorship from Aarhus University Denmark, and is a journal editor for Springer Nature. M.S. reports grant support from Biogen, Astellas, Neurvati Neurosciences, Bridgebio, and Aucta. He has served on scientific advisory boards for Neurogene, Jaguar Gene Therapy and Noema. EBK has received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia, Avexis, Ionis, Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to consult on trial design or development strategies and/or conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, and from Asuragen Inc to develop testing standards for FMR1 testing. All funding to EBK is directed to Rush University Medical Center to support rare disease programs. EBK receives no personal funds. The remaining authors declare that they have no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans. METHODS: A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups. RESULTS: All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning. CONCLUSIONS: Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09600-0 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
in Journal of Neurodevelopmental Disorders > 17 (2025)
[article] Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns [texte imprimé] / Hailey SILVER, Auteur ; Rori GREENBERG, Auteur ; Paige M. SIPER, Auteur ; Jessica ZWEIFACH, Auteur ; Renee SOUFER, Auteur ; Mustafa SAHIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Alexander KOLEVZON, Auteur ; Dorothy E. GRICE, Auteur ; Joseph D. BUXBAUM, Auteur ; Tess LEVY, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 17 (2025)
| Mots-clés : |
Humans Autism Spectrum Disorder/genetics/physiopathology Male Female Nerve Tissue Proteins/genetics Child Child, Preschool Chromosome Disorders/genetics/physiopathology Developmental Disabilities/genetics/physiopathology Adolescent Attention Deficit Disorder with Hyperactivity/genetics Intellectual Disability/genetics Chromosomes, Human, Pair 22/genetics Adult Cohort Studies Chromosome Deletion Autism spectrum disorder Developmental delay Intellectual and developmental disability Phenotype SHANK2 Medicine at Mount Sinai’s Institutional Review Board (IRB) approved the study. Caregivers or legal guardians of the participants provided informed consent, and assent was obtained when applicable. Consent for publication: Not applicable. Competing interests: A.K. receives research support from AMO Pharma and consults for Acadia, Alkermes, Neuren, and GW Pharma. He serves on Scientific Advisory Boards for Ovid Therapeutics, Jaguar Therapeutics, and Ritrova Therapeutics. P.M.S. and Mount Sinai licensed the SAND developed by P.M.S. to Stoelting, Co. J.D.B. holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary professorship from Aarhus University Denmark, and is a journal editor for Springer Nature. M.S. reports grant support from Biogen, Astellas, Neurvati Neurosciences, Bridgebio, and Aucta. He has served on scientific advisory boards for Neurogene, Jaguar Gene Therapy and Noema. EBK has received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia, Avexis, Ionis, Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to consult on trial design or development strategies and/or conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, and from Asuragen Inc to develop testing standards for FMR1 testing. All funding to EBK is directed to Rush University Medical Center to support rare disease programs. EBK receives no personal funds. The remaining authors declare that they have no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans. METHODS: A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups. RESULTS: All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning. CONCLUSIONS: Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09600-0 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
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