AON-based degradation of c.151C>T mutant COCH transcripts associated with dominantly inherited hearing impairment DFNA9.

ABSTRACT: The c.151C>T founder mutation in COCH is a frequent cause of late-onset, dominantly inherited hearing impairment and vestibular dysfunction (DFNA9) in the Dutch/Belgian population. The initial clinical symptoms only manifest between the 3rd and 5th decade of life, which leaves ample time for therapeutic intervention. The dominant inheritance pattern and established non-haploinsufficiency disease mechanism indicate that suppressing translation of mutant COCH transcripts has high therapeutic potential. Single-molecule real-time (SMRT) sequencing resulted in the identification of 11 variants with a low population frequency (<10%) that are specific to the c.151C>T mutant COCH allele. Proof of concept was obtained that gapmer antisense oligonucleotides (AONs), directed agai

SUBMITTER: de Vrieze E 

PROVIDER: S-EPMC7985667 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature