Functional analysis of a de novo variant in the neurodevelopment and generalized epilepsy disease gene NBEA.
Mol Genet Metab
; 134(1-2): 195-202, 2021.
Article
em En
| MEDLINE
| ID: mdl-34412939
ABSTRACT
Neurobeachin (NBEA) was initially identified as a candidate gene for autism. Recently, variants in NBEA have been associated with neurodevelopmental delay and childhood epilepsy. Here, we report on a novel NBEA missense variant (c.5899G > A, p.Gly1967Arg) in the Domain of Unknown Function 1088 (DUF1088) identified in a child enrolled in the Undiagnosed Diseases Network (UDN), who presented with neurodevelopmental delay and seizures. Modeling of this variant in the Caenorhabditis elegans NBEA ortholog, sel-2, indicated that the variant was damaging to in vivo function as evidenced by altered cell fate determination and trafficking of potassium channels in neurons. The variant effect was indistinguishable from that of the reference null mutation suggesting that the variant is a strong hypomorph or a complete loss-of-function. Our experimental data provide strong support for the molecular diagnosis and pathogenicity of the NBEA p.Gly1967Arg variant and the importance of the DUF1088 for NBEA function.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Proteínas de Transporte
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Epilepsia
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Transtornos do Neurodesenvolvimento
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Proteínas do Tecido Nervoso
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Child
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article