H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating
Abstract
:1. Introduction
2. Results
2.1. Mutation Analysis
2.2. H1153Y-Kv11.1 CHANNEL Proteins Have Similar Trafficking Phenotype to WT-Kv11.1 Channel Proteins: Similar Surface Expression and Glycosylation Level
2.3. Electrophysiological Characterization of the Mutation H1153Y in hERG Channel
3. Discussion
4. Material and Methods
4.1. Case Description
4.2. Genetic Analysis
4.3. Plasmid Construct, Cell Cultures, and Transient Transfection in HEK293 Cells
4.4. Immunofluorescence Staining and Microscope Imaging
4.5. Flow Cytometry Assay of Surface Kv11.1 Channel
4.6. Western Blot Analysis and Stain Free Quantification
4.7. Electrophysiological Recording
4.8. Statistical Analysis
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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DNA Change (cDNA) | Protein | Frequency of Variant (GnomAD) | Mutation Tester | SIFT Prediction | Polyphen-2 | Previously Reported in Patients (HGMD) and Phenotype | ACMG |
---|---|---|---|---|---|---|---|
c.3457C > T | P.H1153Y | 0.0048% | Disease causing | Deleterious | Probably damaging (0.981) | Yes/LQTs [22] | 3 [24] |
Study | Phenotype | Variant | Current Density |
---|---|---|---|
pA/pF | |||
This study | SADS | WT | 58.3 ± 14.6 (19) |
H1153Y | 18.7 ± 5.1 * (23) | ||
WT + H153Y | 55.7 ± 20.4 (8) | ||
Anderson et al., 2014 [18] | WT | 97.7 ± 6.2 (9) | |
LQT2 patient (0–90 y.o) | R1005Q | 97.7 ± 6.2 (7) | |
LQT2 patient (0–90 y.o) | L1049P | 34.6 ± 4.5 (7) | |
LQT2 patient (0–90 y.o) | L1066V | 74.3 ± 8.7 (6) | |
Biliczki et al., 2008 [20] | WT | 8.0 ± 1.0(13) | |
Macrolide-induced QT prolongation, asymptomatic | R954C | 4.2 ± 1.2 * (5) | |
Survived SCD, no syncope | G1036D | 6.3 ± 1.4 * (7) | |
Anson et al., 2004 [33] | WT | 94.4 ± 18.3 (19) | |
SNP in SIDS cohort | K897T | 57.3 ± 7.2 (22) | |
SNP in SIDS cohort | P967L | 116.9 ± 18.3 (20) | |
SNP in SIDS cohort | R1047L | 129.5 ± 14.5 (20) | |
SNP in SIDS cohort | Q1068R | 126.1 ± 13.9 (20) |
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Farrugia, A.; Rollet, K.; Sinniger, J.; Brun, S.; Spenle, C.; Ludes, B.; Taleb, O.; Mensah-Nyagan, A.G. H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating. Int. J. Mol. Sci. 2021, 22, 9235. https://doi.org/10.3390/ijms22179235
Farrugia A, Rollet K, Sinniger J, Brun S, Spenle C, Ludes B, Taleb O, Mensah-Nyagan AG. H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating. International Journal of Molecular Sciences. 2021; 22(17):9235. https://doi.org/10.3390/ijms22179235
Chicago/Turabian StyleFarrugia, Audrey, Kevin Rollet, Jérome Sinniger, Susana Brun, Caroline Spenle, Bertrand Ludes, Omar Taleb, and Ayikoe Guy Mensah-Nyagan. 2021. "H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating" International Journal of Molecular Sciences 22, no. 17: 9235. https://doi.org/10.3390/ijms22179235
APA StyleFarrugia, A., Rollet, K., Sinniger, J., Brun, S., Spenle, C., Ludes, B., Taleb, O., & Mensah-Nyagan, A. G. (2021). H1153Y-KCNH2 Mutation Identified in a Sudden Arrhythmic Death Syndrome Case Alters Channel Gating. International Journal of Molecular Sciences, 22(17), 9235. https://doi.org/10.3390/ijms22179235