De Novo variants in EEF2 cause a neurodevelopmental disorder with benign external hydrocephalus.
Hum Mol Genet
; 29(24): 3892-3899, 2021 02 25.
Article
em En
| MEDLINE
| ID: mdl-33355653
ABSTRACT
Eukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder (NDD). Individuals shared a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly. Populational data and bioinformatic analysis underscored the pathogenicity of all de novo missense variants. The eEF2 yeast model strains demonstrated that patient-derived variants affect cellular growth, sensitivity to translation inhibitors and translational fidelity. Consequently, we propose that pathogenic variants in the EEF2 gene, so far exclusively associated with late-onset SCA26, can cause a broader spectrum of neurologic disorders, including childhood-onset NDDs and benign external hydrocephalus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinase do Fator 2 de Elongação
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Exoma
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Transtornos do Neurodesenvolvimento
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Heterozigoto
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Hidrocefalia
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Mutação
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Child
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Child, preschool
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article