USH2A Usher syndrome minigene splice assay non-canonical splice site pre-mRNA splicing retinitis pigmentosa. In addition, cases with these specific variants may now receive a conclusive genetic diagnosis. This type of variant generally should not be neglected in genetic screening, both in USH2A-associated disease as well as other hereditary disorders. We demonstrated that non-canonical splice site variants in USH2A are an important contributor to the genetic etiology of the associated disorders. Various events, such as exon skipping, dual exon skipping and partial exon skipping were observed and eight of the tested variants had a full effect on splicing as no conventionally spliced mRNA was detected. An effect on pre-mRNA splicing was observed for all 11 variants. Ten different USH2A constructs were generated and minigene splice assays were performed in HEK293T cells. Eleven non-canonical splice site variants were selected based on four splice prediction tools. In this study, we aimed to extend the knowledge regarding splicing events by assessing a selected set of USH2A non-canonical splice site variants and to study their potential pathogenicity. Many non-canonical splice site variants have been reported in public databases, but an effect on pre-mRNA splicing has only been functionally verified for a subset of these variants. Non-canonical splice site variants are increasingly recognized as a relevant cause of the USH2A-associated diseases, non-syndromic autosomal recessive retinitis pigmentosa and Usher syndrome type 2.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |