Ataxia-telangiectasia mutated pre-mRNA aberrant splice site (ATM pre-mRNA aberrant splice site)

The Ataxia-telangiectasia mutated (ATM) pre-mRNA aberrant splice site is a specific sequence within the ATM gene's primary transcript that arises from mutations, typically deep intronic, which disrupt normal RNA processing (Cavalieri et al., 2013, PMID: 23532861). These mutations often create cryptic splice donor or acceptor sites, leading to the inclusion of pseudoexons that introduce premature stop codons or frame shifts, ultimately preventing the synthesis of functional ATM protein (UniProt Q13315). The resulting loss of ATM protein severely impairs the DNA damage response, as ATM is a master regulator kinase for double-strand break repair (Shiloh & Ziv, 2013, PMID: 23412070). This deficiency causes Ataxia-telangiectasia, a rare autosomal recessive disorder characterized by cerebellar ataxia, immune deficiency, and increased cancer predisposition (StatPearls, NBK482480). As a therapeutic target, the aberrant splice site is addressed using antisense oligonucleotides (ASOs) that bind specifically to the mutant sequence to sterically block the spliceosome (Kim et al., 2023, PMID: 37468474). By preventing the recognition of the cryptic site, these therapies aim to restore normal splicing patterns and increase the production of functional ATM protein.

Other names

ATM cryptic splice siteATM pseudoexonATM deep intronic mutation siteATM splice-switching target

Splice modulation via steric blocking of cryptic splice sites to restore canonical mRNA processing.