X-Linked Retinitis Pigmentosa Caused by Non-Canonical Splice Site Variants in RPGR.
Friederike Charlotte KortümSinja KieningerPascale MazzolaSusanne KohlBernd WissingerHolger ProkischKatarina StinglNicole WeisschuhPublished in: International journal of molecular sciences (2021)
We aimed to validate the effect of non-canonical splice site variants in the RPGR gene in five patients from four families diagnosed with retinitis pigmentosa. Four variants located in intron 2 (c.154 + 3_154 + 6del), intron 3 (c.247 + 5G>A), intron 7 (c.779-5T>G), and intron 13 (c.1573-12A>G), respectively, were analyzed by means of in vitro splice assays. Splicing analysis revealed different aberrant splicing events, including exon skipping and intronic nucleotide addition, which are predicted to lead either to an in-frame deletion affecting relevant protein domains or to a frameshift of the open reading frame. Our data expand the landscape of pathogenic variants in RPGR, thereby increasing the genetic diagnostic rate in retinitis pigmentosa and allowing patients harboring the analyzed variants to be enrolled in clinical trials.
Keyphrases
- copy number
- end stage renal disease
- clinical trial
- ejection fraction
- newly diagnosed
- chronic kidney disease
- genome wide
- peritoneal dialysis
- randomized controlled trial
- single cell
- prognostic factors
- gene expression
- small molecule
- high throughput
- patient reported outcomes
- electronic health record
- deep learning
- working memory
- open label