5'-UTR SNP of FGF13 causes translational defect and intellectual disability.
Elife
; 102021 06 29.
Article
em En
| MEDLINE
| ID: mdl-34184986
ABSTRACT
The congenital intellectual disability (ID)-causing gene mutations remain largely unclear, although many genetic variations might relate to ID. We screened gene mutations in Chinese Han children suffering from severe ID and found a single-nucleotide polymorphism (SNP) in the 5'-untranslated region (5'-UTR) of fibroblast growth factor 13 (FGF13) mRNA (NM_001139500.1c.-32c>G) shared by three male children. In both HEK293 cells and patient-derived induced pluripotent stem cells, this SNP reduced the translation of FGF13, which stabilizes microtubules in developing neurons. Mice carrying the homologous point mutation in 5'-UTR of Fgf13 showed delayed neuronal migration during cortical development, and weakened learning and memory. Furthermore, this SNP reduced the interaction between FGF13 5'-UTR and polypyrimidine-tract-binding protein 2 (PTBP2), which was required for FGF13 translation in cortical neurons. Thus, this 5'-UTR SNP of FGF13 interferes with the translational process of FGF13 and causes deficits in brain development and cognitive functions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutação Puntual
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Regiões 5' não Traduzidas
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Polimorfismo de Nucleotídeo Único
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Fatores de Crescimento de Fibroblastos
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Deficiência Intelectual
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
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Animals
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Child
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Child, preschool
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Humans
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Male
Idioma:
En
Revista:
Elife
Ano de publicação:
2021
Tipo de documento:
Article