X-Linked Retinitis Pigmentosa Caused by Non-Canonical Splice Site Variants in RPGR

International Journal of Molecular Sciences

卷:22

Nicole Weisschuh¹  Bernd Wissinger¹  Susanne Kohl¹  Sinja Kieninger¹  Katarina Stingl²  Friederike Kortüm²  Pascale Mazzola³  Holger Prokisch⁴ 

[1] Center for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany;

[2] Center for Ophthalmology, University Eye Hospital, University of Tübingen, 72076 Tübingen, Germany;

[3] Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany;

[4] Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;

关键词: retinitis pigmentosa;    X-linked;    RPGR;    non-canonical splice site variant;    in vitro splice assay;   

DOI  :  10.3390/ijms22020850

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown