Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants
Abstract
:1. Introduction
2. Results
2.1. Clinical Phenotype
2.2. Validation of Variants
3. Discussion
4. Materials and Methods
4.1. Patient Enrollment and Retrieval of Blood Samples
4.2. Clinical Evaluation
4.3. Genetic Diagnostic Testing
4.4. In Silico Analysis
4.5. In Vitro Splice Assays
4.6. Direct mRNA Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient | cDNA (NM_172240.3) | Protein (NP_758440.1) | Zygosity | Trans Config. Validated | gnomAD MAF | SpliceAI Prediction (0–1) | NNSplice Prediction (0–1) |
---|---|---|---|---|---|---|---|
CRD766 | c.1331_1332dup | p.(T445Rfs*10) | hom | no | - | N/A | N/A |
MDS438 | c.810+1G>T | p.(V226Gfs*30) AND p.(F188Dfs*73) | het | yes | 2.715E-05 | Donor loss (0.99) | Wildtype donor not recognized |
c.1033-327T>A | p.(I345Afs*9) | het | 4.789E-05 | Acceptor gain (0.6) | Acceptor gain (0.61) | ||
CRD668 | c.561-3T>C | p.(F188Sfs*6) | het | no | - | Acceptor loss (0.21) | No effect |
c.1340C>G | p.(S447*) | het | - | N/A | N/A |
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Weisschuh, N.; Mazzola, P.; Bertrand, M.; Haack, T.B.; Wissinger, B.; Kohl, S.; Stingl, K. Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants. Int. J. Mol. Sci. 2021, 22, 5396. https://doi.org/10.3390/ijms22105396
Weisschuh N, Mazzola P, Bertrand M, Haack TB, Wissinger B, Kohl S, Stingl K. Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants. International Journal of Molecular Sciences. 2021; 22(10):5396. https://doi.org/10.3390/ijms22105396
Chicago/Turabian StyleWeisschuh, Nicole, Pascale Mazzola, Miriam Bertrand, Tobias B. Haack, Bernd Wissinger, Susanne Kohl, and Katarina Stingl. 2021. "Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants" International Journal of Molecular Sciences 22, no. 10: 5396. https://doi.org/10.3390/ijms22105396