Identification and characterization of a novel intronic splicing mutation in CSF1R‐related leukoencephalopathy

Abstract

AbstractAimsColony 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.MethodsA 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.ResultsA 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.ConclusionsOur findings underscore the importance of intronic mis‐splicing mutations in the diagnosis and management of CSF1R‐related leukoencephalopathy.