Neurofibromin 1 (<i>NF1</i>) Splicing Mutation c.61-2A>G: From Aberrant mRNA Processing to Therapeutic Implications In Silico.

ABSTRACT: The neurofibromin 1 (NF1) splice-site mutation c.61-2A>G (rs1131691100) is a rare, pathogenic, autosomal dominant variant that disrupts NF1 tumor-suppressor function, causing neurofibromatosis type 1 (NF1). Its pathogenic mechanism is poorly understood, and the potential for personalized therapeutic genome editing remains unknown due to the absence of a standard framework for investigating splicing disorders. Here, we performed a comprehensive multi-omics analysis of a de novo c.61-2A>G case from South Korea, integrating short- and long-read whole genome sequencing, whole transcriptome sequencing, and methylation profiling. We confirm that c.61-2A>G abolishes the canonical splice acceptor site, activating a cryptic splice acceptor 16 nucleotides downstream in exon 2. This spl

SUBMITTER: Blazyte A 

PROVIDER: S-EPMC12898238 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature