Stargardt disease-associated in-frame ABCA4 exon 17 skipping results in significant ABCA4 function.

ABSTRACT:

Background

ABCA4, the gene implicated in Stargardt disease (STGD1), contains 50 exons, of which 17 contain multiples of three nucleotides. The impact of in-frame exon skipping is yet to be determined. Antisense oligonucleotides (AONs) have been investigated in Usher syndrome-associated genes to induce skipping of in-frame exons carrying severe variants and mitigate their disease-linked effect. Upon the identification of a STGD1 proband carrying a novel exon 17 canonical splice site variant, the activity of ABCA4 lacking 22 amino acids encoded by exon 17 was examined, followed by design of AONs able to induce exon 17 skipping.

Methods

A STGD1 proband was compound heterozygous for the splice variant c.2653+1G>A, that was predicted to result in in-frame skipping of exon 17, and

SUBMITTER: Kaltak M 

PROVIDER: S-EPMC10428568 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature