Variants in BSN , encoding the presynaptic protein Bassoon, result in a novel neurodevelopmental disorder with a broad phenotypic range
Rattachement africain : us, au, es, nl, fr, ca. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders and epilepsy. Here, we describe 14 individuals with de novo disruptive variants in BSN , which encodes the presynaptic protein Bassoon. To expand the phenotypic spectrum, we identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks. Clinical features were standardized using the Human Phenotype Ontology (HPO) across all 29 individuals, which revealed common clinical characteristics including epilepsy (13/29 45%), febrile seizures (7/29 25%), generalized tonic-clonic seizures (5/29 17%), and focal onset seizures (3/29 10%). Behavioral phenotypes were present in almost half of all individuals (14/29 48%), which comprised ADHD (7/29 25%) and autistic behavior (5/29 17%). Additional common features included developmental delay (11/29 38%), obesity (10/29 34%), and delayed speech (8/29 28%). In adults with BSN PTVs, milder features were common, suggesting phenotypic variability including a range of individuals without obvious neurodevelopmental features (7/29 24%). To detect gene-specific signatures, we performed association analysis in a cohort of 14,895 individuals with neurodevelopmental disorders (NDDs). A total of 66 clinical features were associated with BSN , including febrile seizures (p=1.26e-06) and behavioral disinhibition (p = 3.39e-17). Furthermore, individuals carrying BSN variants were phenotypically more similar than expected by chance (p=0.00014), exceeding phenotypic relatedness in 179/256 NDD-related conditions. In summary, integrating information derived from community-based gene matching and large data repositories through computational phenotyping approaches, we identify BSN variants as the cause of a new class of synaptic disorder with a broad phenotypic range across the age spectrum.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Variants in <i>BSN</i> , encoding the presynaptic protein Bassoon, result in a novel neurodevelopmental disorder with a broad phenotypic range
- Date Crossref
- 12/02/2025
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Children's Hospital of Philadelphia The Epilepsy NeuroGenetics Initiative (ENGIN) pays non établi dans la noticeOrganisme public
-
University of Pennsylvania Department of Biochemistry pays non établi dans la noticeUniversité ou école supérieure
-
The University of Melbourne Department of Paediatrics pays non établi dans la noticeUniversité ou école supérieure
-
Victorian Clinical Genetics Services pays non établi dans la noticeStructure de recherche
-
Murdoch Children's Research Institute pays non établi dans la noticeOrganisation à but non lucratif
-
Melbourne Genomics Health Alliance pays non établi dans la noticeOrganisation à but non lucratif
-
Australian Genomics Health Alliance pays non établi dans la noticeOrganisation à but non lucratif
-
Miami Children's Hospital pays non établi dans la noticeÉtablissement de santé
-
Hospital Universitario La Paz pays non établi dans la noticeÉtablissement de santé
-
Instituto de Salud Carlos III Centre for Biomedical Network Research on Rare Diseases (CIBERER) pays non établi dans la noticeOrganisme public
-
Centre for Biomedical Network Research on Rare Diseases pays non établi dans la noticeStructure de recherche
-
ERN GUARD-Heart pays non établi dans la noticeÉtablissement de santé
The Epilepsy NeuroGenetics Initiative (ENGIN) — Children's Hospital of Philadelphia, Department of Biochemistry — University of Pennsylvania et Department of Paediatrics — The University of Melbourne, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.