Identification and characterization of a novel intronic splicing mutation in CSF1R-related leukoencephalopathy.
CNS Neurosci Ther
; 30(6): e14815, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38922778
ABSTRACT
AIMS:
Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressing neurodegenerative disease caused by CSF1R gene mutations. This study aimed to identify and investigate the effect of a novel intronic mutation (c.1754-3C>G) of CSF1R on splicing.METHODS:
A novel intronic mutation was identified using whole-exome sequencing. To investigate the impact of this mutation, we employed various bioinformatics tools to analyze the transcription of the CSF1R gene and the three-dimensional structure of its encoded protein. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the findings.RESULTS:
A novel mutation (c.1754-3C>G) in CSF1R was identified, which results in exon 13 skipping due to the disruption of the 3' splice site consensus sequence NYAG/G. This exon skipping event was further validated in the peripheral blood of the mutation carrier through RT-PCR and Sanger sequencing. Protein structure prediction indicated a disruption in the tyrosine kinase domain, with the truncated protein showing significant structural alterations.CONCLUSIONS:
Our findings underscore the importance of intronic mis-splicing mutations in the diagnosis and management of CSF1R-related leukoencephalopathy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Íntrons
/
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos
/
Leucoencefalopatias
/
Mutação
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
CNS Neurosci Ther
Assunto da revista:
NEUROLOGIA
/
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China