Usher syndrome type 2A (USH2A) exon 13 genomic DNA locus (USH2A exon 13)

The Usher syndrome type 2A (USH2A) exon 13 genomic DNA locus is a specific segment of the USH2A gene (NCBI Gene: 7399) that encodes usherin, a protein vital for the structural integrity of retinal photoreceptors and inner ear hair cells (UniProt: O75445). Usherin is localized to the photoreceptor connecting cilium, where it supports protein transport and cellular stability. Mutations within this locus, such as the prevalent c.2299delG frameshift, are primary causes of Usher syndrome type IIa and autosomal recessive retinitis pigmentosa (PubMed: 25539965). This locus is a significant therapeutic target because exon 13 is "in-frame," meaning its removal via antisense oligonucleotides (ASOs) or gene editing can result in a truncated but functional protein. The ASO ultevursen (QR-421a) was developed to induce exon 13 skipping to treat vision loss in these patients (ProQR Therapeutics). Additionally, CRISPR-based strategies like EDIT-103 aim to correct or delete mutations at this genomic site (Editas Medicine). Therapeutic challenges include the need for precise subretinal delivery and the management of potential inflammatory responses to viral vectors or ASOs.

Other names

Usherin gene exon 13USH2A c.2299delG locusUSH2A exon 13

Antisense oligonucleotide-mediated exon skipping and CRISPR-based gene editing