Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome
Background - A variant in the SLC4A3 anion exchanger has been identified as a novel cause of short QT syndrome (SQTS), but the clinical importance of SLC4A3 as a cause of SQTS or sudden cardiac death remains unknown. - Objective - The purpose of this study was to investigate the prevalence of potent...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 2023
|
| In: |
Heart rhythm
Year: 2023, Volume: 20, Issue: 8, Pages: 1136-1143 |
| ISSN: | 1556-3871 |
| DOI: | 10.1016/j.hrthm.2023.02.010 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.hrthm.2023.02.010 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1547527123001480 
|
| Author Notes: | Morten Krogh Christiansen, MD, PhD, Kasper Kjær-Sørensen, PhD, Natacha C. Clavsen, MSc, Sven Dittmann, PhD, Maja Fuhlendorff Jensen, MSc, Halvor Østerby Guldbrandsen, BMed, Lisbeth Nørum Pedersen, MSc, PhD, Rikke Hasle Sørensen, MSc, Dorte Launholt Lildballe, MSc, PhD, Klara Müller, MSc, Patrick Müller, MD, Kira Vogel, MStud, Boris Rudic, MD, Martin Borggrefe, MD, Claus Oxvig, PhD, Christian Aalkjær, MD, DMSc, Eric Schulze-Bahr, MD, PhD, Vladimir Matchkov, PhD, DMSc, Henning Bundgaard, MD, DMSc, Henrik Kjærulf Jensen, MD, PhD, DMSc |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1884601103 | ||
| 003 | DE-627 | ||
| 005 | 20240703161350.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240328s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.hrthm.2023.02.010 |2 doi | |
| 035 | |a (DE-627)1884601103 | ||
| 035 | |a (DE-599)KXP1884601103 | ||
| 035 | |a (OCoLC)1443667996 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Christiansen, Morten Krogh |e VerfasserIn |0 (DE-588)1324721677 |0 (DE-627)1884601731 |4 aut | |
| 245 | 1 | 0 | |a Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome |c Morten Krogh Christiansen, MD, PhD, Kasper Kjær-Sørensen, PhD, Natacha C. Clavsen, MSc, Sven Dittmann, PhD, Maja Fuhlendorff Jensen, MSc, Halvor Østerby Guldbrandsen, BMed, Lisbeth Nørum Pedersen, MSc, PhD, Rikke Hasle Sørensen, MSc, Dorte Launholt Lildballe, MSc, PhD, Klara Müller, MSc, Patrick Müller, MD, Kira Vogel, MStud, Boris Rudic, MD, Martin Borggrefe, MD, Claus Oxvig, PhD, Christian Aalkjær, MD, DMSc, Eric Schulze-Bahr, MD, PhD, Vladimir Matchkov, PhD, DMSc, Henning Bundgaard, MD, DMSc, Henrik Kjærulf Jensen, MD, PhD, DMSc |
| 264 | 1 | |c August 2023 | |
| 300 | |b Illustrationen | ||
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar: 15. Februar 2023, Artikelversion: 28. Juli 2023 | ||
| 500 | |a Gesehen am 28.03.2024 | ||
| 520 | |a Background - A variant in the SLC4A3 anion exchanger has been identified as a novel cause of short QT syndrome (SQTS), but the clinical importance of SLC4A3 as a cause of SQTS or sudden cardiac death remains unknown. - Objective - The purpose of this study was to investigate the prevalence of potential disease-causing variants in SQTS patients using gene panels including SLC4A3. - Methods - In this multicenter study, genetic testing was performed in 34 index patients with SQTS. The pathogenicity of novel SLC4A3variants was validated in a zebrafish embryo heart model. - Results - Potentially disease-causing variants were identified in 9 (26%) patients and were mainly (15%) located in SLC4A3: 4 patients heterozygous for novel nonsynonymous SLC4A3 variants—p.Arg600Cys, p.Arg621Trp, p.Glu852Asp, and p.Arg952His—and 1 patient with the known p.Arg370His variant. In other SQTS genes, potentially disease-causing variants were less frequent (2× in KCNQ1, 1× in KCNJ2, and CACNA1C each). SLC4A3 variant carriers (n = 5) had a similar heart rate but shorter QT and J point to T wave peak intervals than did noncarriers (n = 29). Knockdown of slc4a3 in zebrafish resulted in shortened heart rate-corrected QT intervals (calculated using the Bazett formula) that could be rescued by overexpression of the native human SLC4A3-encoded protein (AE3), but neither by the mutated AE3 variants p.Arg600Cys, p.Arg621Trp, p.Glu852Asp nor by p.Arg952His, suggesting pathogenicity of these variants. Dysfunction in slc4a3/AE3 was associated with alkaline cytosol and shortened action potential of cardiomyocytes. - Conclusion - In about a quarter of patients with SQTS, a potentially disease-causing variant can be identified. Nonsynonymous variants in SLC4A3 represent the most common cause of SQTS, underscoring the importance of including SLC4A3 in the genetic screening of patients with SQTS or sudden cardiac death. | ||
| 650 | 4 | |a Genetic testing | |
| 650 | 4 | |a Heart model | |
| 650 | 4 | |a Mutation | |
| 650 | 4 | |a QT interval | |
| 650 | 4 | |a Short QT syndrome | |
| 650 | 4 | |a Zebrafish | |
| 700 | 1 | |a Kjær-Sørensen, Kasper |e VerfasserIn |4 aut | |
| 700 | 1 | |a Clavsen, Natacha C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dittmann, Sven |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jensen, Maja Fuhlendorff |e VerfasserIn |4 aut | |
| 700 | 1 | |a Guldbrandsen, Halvor Østerby |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pedersen, Lisbeth Nørum |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sørensen, Rikke Hasle |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lildballe, Dorte Launholt |e VerfasserIn |4 aut | |
| 700 | 1 | |a Müller, Klara |e VerfasserIn |4 aut | |
| 700 | 1 | |a Müller, Patrick |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vogel, Kira |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rudic, Boris |d 1982- |e VerfasserIn |0 (DE-588)1024726789 |0 (DE-627)720427134 |0 (DE-576)369410599 |4 aut | |
| 700 | 1 | |a Borggrefe, Martin |e VerfasserIn |0 (DE-588)1025920546 |0 (DE-627)725574232 |0 (DE-576)370913426 |4 aut | |
| 700 | 1 | |a Oxvig, Claus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Aalkjær, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schulze-Bahr, Eric |e VerfasserIn |4 aut | |
| 700 | 1 | |a Matchkov, Vladimir |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bundgaard, Henning |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jensen, Henrik Kjærulf |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Heart rhythm |d New York, NY [u.a.] : Elsevier, 2004 |g 20(2023), 8 vom: Aug., Seite 1136-1143 |h Online-Ressource |w (DE-627)391333739 |w (DE-600)2152161-X |w (DE-576)309205557 |x 1556-3871 |7 nnas |a Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome |
| 773 | 1 | 8 | |g volume:20 |g year:2023 |g number:8 |g month:08 |g pages:1136-1143 |g extent:8 |a Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.hrthm.2023.02.010 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S1547527123001480 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240328 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 1025920546 |a Borggrefe, Martin |m 1025920546:Borggrefe, Martin |d 60000 |d 61000 |e 60000PB1025920546 |e 61000PB1025920546 |k 0/60000/ |k 1/60000/61000/ |p 14 | ||
| 998 | |g 1024726789 |a Rudic, Boris |m 1024726789:Rudic, Boris |d 60000 |d 61000 |e 60000PR1024726789 |e 61000PR1024726789 |k 0/60000/ |k 1/60000/61000/ |p 13 | ||
| 999 | |a KXP-PPN1884601103 |e 4505276686 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Morten Krogh Christiansen, MD, PhD, Kasper Kjær-Sørensen, PhD, Natacha C. Clavsen, MSc, Sven Dittmann, PhD, Maja Fuhlendorff Jensen, MSc, Halvor Østerby Guldbrandsen, BMed, Lisbeth Nørum Pedersen, MSc, PhD, Rikke Hasle Sørensen, MSc, Dorte Launholt Lildballe, MSc, PhD, Klara Müller, MSc, Patrick Müller, MD, Kira Vogel, MStud, Boris Rudic, MD, Martin Borggrefe, MD, Claus Oxvig, PhD, Christian Aalkjær, MD, DMSc, Eric Schulze-Bahr, MD, PhD, Vladimir Matchkov, PhD, DMSc, Henning Bundgaard, MD, DMSc, Henrik Kjærulf Jensen, MD, PhD, DMSc"]},"id":{"doi":["10.1016/j.hrthm.2023.02.010"],"eki":["1884601103"]},"origin":[{"dateIssuedDisp":"August 2023","dateIssuedKey":"2023"}],"relHost":[{"disp":"Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndromeHeart rhythm","physDesc":[{"extent":"Online-Ressource"}],"recId":"391333739","language":["eng"],"type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 01.11.11"],"id":{"zdb":["2152161-X"],"eki":["391333739"],"issn":["1556-3871"]},"part":{"pages":"1136-1143","text":"20(2023), 8 vom: Aug., Seite 1136-1143","extent":"8","issue":"8","year":"2023","volume":"20"},"title":[{"title":"Heart rhythm","title_sort":"Heart rhythm"}],"origin":[{"dateIssuedKey":"2004","dateIssuedDisp":"2004-","publisherPlace":"New York, NY [u.a.]","publisher":"Elsevier"}],"pubHistory":["1.2004 -"]}],"person":[{"family":"Christiansen","given":"Morten Krogh","role":"aut","display":"Christiansen, Morten Krogh"},{"display":"Kjær-Sørensen, Kasper","family":"Kjær-Sørensen","given":"Kasper","role":"aut"},{"given":"Natacha C.","role":"aut","family":"Clavsen","display":"Clavsen, Natacha C."},{"display":"Dittmann, Sven","family":"Dittmann","role":"aut","given":"Sven"},{"display":"Jensen, Maja Fuhlendorff","family":"Jensen","role":"aut","given":"Maja Fuhlendorff"},{"display":"Guldbrandsen, Halvor Østerby","role":"aut","given":"Halvor Østerby","family":"Guldbrandsen"},{"family":"Pedersen","role":"aut","given":"Lisbeth Nørum","display":"Pedersen, Lisbeth Nørum"},{"family":"Sørensen","role":"aut","given":"Rikke Hasle","display":"Sørensen, Rikke Hasle"},{"family":"Lildballe","given":"Dorte Launholt","role":"aut","display":"Lildballe, Dorte Launholt"},{"family":"Müller","given":"Klara","role":"aut","display":"Müller, Klara"},{"display":"Müller, Patrick","role":"aut","given":"Patrick","family":"Müller"},{"role":"aut","given":"Kira","family":"Vogel","display":"Vogel, Kira"},{"display":"Rudic, Boris","given":"Boris","role":"aut","family":"Rudic"},{"given":"Martin","role":"aut","family":"Borggrefe","display":"Borggrefe, Martin"},{"display":"Oxvig, Claus","family":"Oxvig","role":"aut","given":"Claus"},{"display":"Aalkjær, Christian","family":"Aalkjær","role":"aut","given":"Christian"},{"display":"Schulze-Bahr, Eric","role":"aut","given":"Eric","family":"Schulze-Bahr"},{"display":"Matchkov, Vladimir","family":"Matchkov","given":"Vladimir","role":"aut"},{"display":"Bundgaard, Henning","family":"Bundgaard","given":"Henning","role":"aut"},{"family":"Jensen","given":"Henrik Kjærulf","role":"aut","display":"Jensen, Henrik Kjærulf"}],"title":[{"title_sort":"Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome","title":"Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"language":["eng"],"note":["Online verfügbar: 15. Februar 2023, Artikelversion: 28. Juli 2023","Gesehen am 28.03.2024"],"recId":"1884601103","physDesc":[{"extent":"8 S.","noteIll":"Illustrationen"}]} | ||
| SRT | |a CHRISTIANSGENETICANA2023 | ||