Version 1
: Received: 5 September 2024 / Approved: 6 September 2024 / Online: 9 September 2024 (12:40:34 CEST)
How to cite:
Elasal, M. A.; Khateb, S.; Panneman, D. M.; Roosing, S.; Banin, E.; Sharon, D.; Sarma, A. S. A Leaky Deep Intronic Splice Variant in CLRN1 Is Associated With Non-syndromic Retinitis Pigmentosa. Preprints2024, 2024090569. https://doi.org/10.20944/preprints202409.0569.v1
Elasal, M. A.; Khateb, S.; Panneman, D. M.; Roosing, S.; Banin, E.; Sharon, D.; Sarma, A. S. A Leaky Deep Intronic Splice Variant in CLRN1 Is Associated With Non-syndromic Retinitis Pigmentosa. Preprints 2024, 2024090569. https://doi.org/10.20944/preprints202409.0569.v1
Elasal, M. A.; Khateb, S.; Panneman, D. M.; Roosing, S.; Banin, E.; Sharon, D.; Sarma, A. S. A Leaky Deep Intronic Splice Variant in CLRN1 Is Associated With Non-syndromic Retinitis Pigmentosa. Preprints2024, 2024090569. https://doi.org/10.20944/preprints202409.0569.v1
APA Style
Elasal, M. A., Khateb, S., Panneman, D. M., Roosing, S., Banin, E., Sharon, D., & Sarma, A. S. (2024). A Leaky Deep Intronic Splice Variant in CLRN1 Is Associated With Non-syndromic Retinitis Pigmentosa. Preprints. https://doi.org/10.20944/preprints202409.0569.v1
Chicago/Turabian Style
Elasal, M. A., Dror Sharon and Asodu Sandeep Sarma. 2024 "A Leaky Deep Intronic Splice Variant in CLRN1 Is Associated With Non-syndromic Retinitis Pigmentosa" Preprints. https://doi.org/10.20944/preprints202409.0569.v1
Abstract
Inherited retinal diseases (IRDs) are clinically complex and genetically heterogeneous visual impairment disorders with varying penetrance and severity. Disease-causing variants in at least 289 nuclear and mitochondrial genes have been implicated in their pathogenesis. In the current study, we performed exome sequencing on a 51 years-old Ashkenazi Jewish patient with non-syndromic retinitis pigmentosa (RP) and identified compound heterozygous variants in the CLRN1 gene: a known pathogenic missense [p.(N48K)] and a novel deep intronic variant c.254-643G>T. A minigene splicing assay that was performed aiming to study the effect of the c.254-643G>T variant on CLRN1 pre mRNA splicing revealed the inclusion of a pseudo-exon that was also reported to be included in the transcript due to an adjacent variant, c.254-649T>G. However, unlike the reported c.254-649T>G variant, c.254-643G>T showed aberrant splicing in a leaky manner, implying that the identified variant is not totally penetrant. The non-syndromic phenotype observed in this index case may be attributed to the leaky nature of this variant, which is causing some normal transcripts to be produced. To conclude, we report on a novel deep intronic variant in CLRN1 causing non-syndromic RP.
Keywords
CLRN1; deep intronic; inherited retinal diseases; pseudo-exon; retinitis pigmentosa; splicing
Subject
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
*
,
*
