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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 ADNPpresent 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 ADNPand 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 SMARCA2pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNPvariants. This represents first evidence of a sensitive phenotype‐specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene‐specific episignatures.

Depuis 2013, l’exome est utilisé pour le diagnostic des ataxies cérébelleuses héréditaires quand les examens complémentaires n’ont pas permis d’évoquer d’hypothèses diagnostiques précises et que les analyses moléculaires classiques sont négatives.

Le séquençage de l’exome est un outil diagnostique pangénomique qui a révolutionné la démarche diagnostique. Depuis 2013, il est utilisé dans les maladies neurogénétiques de l’adulte.