A novel missense mutation of RPGR identified from retinitis pigmentosa affects splicing of the ORF15 region and causes loss of transcript heterogeneity

Liu, Yan-Shan; Pan, Jiaji; Wan, Jifeng; Ren, Chunyan; Xu, Zhuangzhuang; Gao, Ruonan; Liu, Shaoqiang; Zhang, Jiali; Yao, Qian-Hao; Wang, Jihong; Li, En‐Min; Rao, Junhua; Hou, Ping; Chen, Jian‐Huan

doi:10.1016/j.bbrc.2020.06.109

Cited by 3 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown previously that 0.8% of RPGR transcripts in the human retina demonstrate exon 12 skipping [38]. Intron 14 retention has been demonstrated in a minigene assay comprising exon 13, intron 13, exon 14, intron 14, and ORF15 [39]. Moreover, intron 14 retention has also been shown to occur in the human retinal pigment epithelium cell line ARPE-19 [39].…”

Section: Discussionmentioning

confidence: 78%

“…Intron 14 retention has been demonstrated in a minigene assay comprising exon 13, intron 13, exon 14, intron 14, and ORF15 [39]. Moreover, intron 14 retention has also been shown to occur in the human retinal pigment epithelium cell line ARPE-19 [39]. When we investigated RNAseq datasets derived from healthy human retina and brain donor samples, we saw evidence of both exon 12 skipping and intron 14 retention.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

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

Kortüm

Kieninger

Mazzola

et al. 2021

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 90%

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

Kortüm

Kieninger

Mazzola

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In addition to histological characterization, retinal transcriptomic analyses through bulk RNA-seq have been widely used to identify the molecular mechanisms underlying pathological processes that cause retinal dystrophies (Bales et al, 2018;Liu et al, 2020;Uren et al, 2014). However, subtle transcriptomic differences between differentiated photoreceptors might go undetected, which is critical while studying the NR2E3 opposing roles in rod and cone transcriptional networks.…”

Section: Introductionmentioning

confidence: 99%

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases

Aísa-Marín,

Rovira,

Díaz

et al. 2023

Preprint

View full text Add to dashboard Cite

Mutations inNR2E3cause two retinal dystrophies with a distinct phenotype.NR2E3encodes an orphan nuclear transcription factor that contributes to photoreceptor cell fate determination by repressing cone while activating rod genes. To dissect NR2E3 function, we performed scRNA-seq in the retinas of wild type and two differentNr2e3mouse models that show phenotypes similar to patients carryingNR2E3mutations. Our results reveal that rod and cone populations are not homogeneous and can be separated into different sub-classes. We identify a previously unreported cone pathway that generates hybrid cones that co-express both cone- and rod-related genes. In mutant retinas, this hybrid cone subpopulation is more abundant, as it includes a subpopulation of rods transitioning towards a cone cell fate. Hybrid photoreceptors with high misexpression of cone- and rod-related genes are prone to regulated necrosis. Overall, our results shed light on the role of NR2E3 in modulating photoreceptor differentiation towards cone and rod fates and explain how mutations inNR2E3lead to different visual disorders in humans.

show abstract

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases

Aísa-Marín,

Rovira,

Díaz

et al. 2024

Neurobiology of Disease

View full text Add to dashboard Cite

A novel missense mutation of RPGR identified from retinitis pigmentosa affects splicing of the ORF15 region and causes loss of transcript heterogeneity

Cited by 3 publications

References 25 publications

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

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

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases

Contact Info

Product

Resources

About