RESUMO
CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.
Assuntos
Deficiências do Desenvolvimento/genética , Epilepsia Generalizada/genética , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Deficiências do Desenvolvimento/fisiopatologia , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/etiologia , Epilepsias Mioclônicas/genética , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/etiologia , Exoma/genética , Feminino , Variação Genética , Humanos , Lactente , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , Masculino , Mutação/genética , Fenótipo , Estado Epiléptico/diagnóstico , Estado Epiléptico/etiologia , Estado Epiléptico/genética , Adulto JovemRESUMO
SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development. However, the phenotypic effects of deleterious germline variants in SON have not been clearly defined. Herein, we describe seven unrelated individuals with de novo variants in SON and propose that deleterious variants in SON are associated with a severe multisystem disorder characterized by developmental delay, persistent feeding difficulties, and congenital malformations, including brain anomalies.
