Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.
ADNP
Helsmoortel‐Van Der Aa Syndrome
SMARCA2
blepharophimosis with intellectual disability
Journal
American journal of medical genetics. Part C, Seminars in medical genetics
ISSN: 1552-4876
Titre abrégé: Am J Med Genet C Semin Med Genet
Pays: United States
ID NLM: 101235745
Informations de publication
Date de publication:
17 Jun 2024
17 Jun 2024
Historique:
revised:
10
04
2024
received:
21
12
2023
accepted:
11
05
2024
medline:
17
6
2024
pubmed:
17
6
2024
entrez:
17
6
2024
Statut:
aheadofprint
Résumé
Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures.
Identifiants
pubmed: 38884529
doi: 10.1002/ajmg.c.32089
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e32089Subventions
Organisme : Telethon Foundation, Telethon Undiagnosed Diseases Program
Organisme : Genome Canada and the Ontario Genomics Institute
Informations de copyright
© 2024 The Author(s). American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.
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