Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2
Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2....
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 December 2010
|
| In: |
Canadian journal of physiology and pharmacology
Year: 2010, Jahrgang: 88, Heft: 12, Pages: 1181-1190 |
| ISSN: | 1205-7541 |
| DOI: | 10.1139/Y10-094 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1139/Y10-094
|
| Verfasserangaben: | Jonathan M. Cordeiro, Guillermo J. Perez, Nicole Schmitt, Ryan Pfeiffer, Vladislav V. Nesterenko, Elena Burashnikov, Christian Veltmann, Martin Borggrefe, Christian Wolpert, Rainer Schimpf, Charles Antzelevitch |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1850471088 | ||
| 003 | DE-627 | ||
| 005 | 20230710130315.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230616s2010 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1139/Y10-094 |2 doi | |
| 035 | |a (DE-627)1850471088 | ||
| 035 | |a (DE-599)KXP1850471088 | ||
| 035 | |a (OCoLC)1389793795 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Cordeiro, Jonathan M. |e VerfasserIn |0 (DE-588)1292914645 |0 (DE-627)1850471983 |4 aut | |
| 245 | 1 | 0 | |a Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2 |c Jonathan M. Cordeiro, Guillermo J. Perez, Nicole Schmitt, Ryan Pfeiffer, Vladislav V. Nesterenko, Elena Burashnikov, Christian Veltmann, Martin Borggrefe, Christian Wolpert, Rainer Schimpf, Charles Antzelevitch |
| 264 | 1 | |c 1 December 2010 | |
| 300 | |a 10 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 16.06.2023 | ||
| 520 | |a Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2. The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4-V6 and LQT1 morphology in leads V1-V2. Genomic DNA was isolated from lymphocytes. All exons and intron borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed patch-clamp analysis. In addition, WT or K897T Kv11.1 were also studied by patch clamp. Current-voltage (I-V) relations for V110I showed a significant reduction in both developing and tail current densities compared with WT at potentials >+20 mV (p < 0.05; n = 8 cells, each group), suggesting a reduction in IKs currents. K897T- Kv11.1 channels displayed a significantly reduced tail current density compared with WT-Kv11.1 at potentials >+10 mV. Interestingly, channel availability assessed using a triple-pulse protocol was slightly greater for K897T compared with WT (V0.5 = -53.1 ± 1.13 mV and -60.7 ± 1.15 mV for K897T and WT, respectively; p < 0.05). Comparison of the fully activated I-V revealed no difference in the rectification properties between WT and K897T channels. We report a patient with a loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest that a reduction of both IKr and IKs underlies the combined LQT1 and LQT2 phenotype observed in this patient. | ||
| 650 | 4 | |a Adult | |
| 650 | 4 | |a Amino Acid Sequence | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Base Sequence | |
| 650 | 4 | |a Cells, Cultured | |
| 650 | 4 | |a CHO Cells | |
| 650 | 4 | |a Cricetinae | |
| 650 | 4 | |a Cricetulus | |
| 650 | 4 | |a Electrocardiography | |
| 650 | 4 | |a ERG1 Potassium Channel | |
| 650 | 4 | |a Ether-A-Go-Go Potassium Channels | |
| 650 | 4 | |a Female | |
| 650 | 4 | |a Genetic Variation | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a KCNQ1 Potassium Channel | |
| 650 | 4 | |a Long QT Syndrome | |
| 650 | 4 | |a Molecular Sequence Data | |
| 650 | 4 | |a Mutation | |
| 650 | 4 | |a Phenotype | |
| 650 | 4 | |a Polymorphism, Genetic | |
| 700 | 1 | |a Perez, Guillermo J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmitt, Nicole |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pfeiffer, Ryan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nesterenko, Vladislav V. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Burashnikov, Elena |e VerfasserIn |4 aut | |
| 700 | 1 | |a Veltmann, Christian |d 1976- |e VerfasserIn |0 (DE-588)124458912 |0 (DE-627)363362541 |0 (DE-576)294181660 |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 Wolpert, Christian |d 1967- |e VerfasserIn |0 (DE-588)122247965 |0 (DE-627)705830284 |0 (DE-576)293172900 |4 aut | |
| 700 | 1 | |a Schimpf, Rainer |d 1966- |e VerfasserIn |0 (DE-588)1025920244 |0 (DE-627)725573767 |0 (DE-576)370912772 |4 aut | |
| 700 | 1 | |a Antzelevitch, Charles |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Canadian journal of physiology and pharmacology |d Ottawa, Ont. : NRC Research Press, 1964 |g 88(2010), 12, Seite 1181-1190 |h Online-Ressource |w (DE-627)320436047 |w (DE-600)2004356-9 |w (DE-576)273865439 |x 1205-7541 |7 nnas |a Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2 |
| 773 | 1 | 8 | |g volume:88 |g year:2010 |g number:12 |g pages:1181-1190 |g extent:10 |a Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2 |
| 856 | 4 | 0 | |u https://doi.org/10.1139/Y10-094 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230616 | ||
| 993 | |a Article | ||
| 994 | |a 2010 | ||
| 998 | |g 1025920244 |a Schimpf, Rainer |m 1025920244:Schimpf, Rainer |d 60000 |e 60000PS1025920244 |k 0/60000/ |p 10 | ||
| 998 | |g 122247965 |a Wolpert, Christian |m 122247965:Wolpert, Christian |d 60000 |d 61000 |e 60000PW122247965 |e 61000PW122247965 |k 0/60000/ |k 1/60000/61000/ |p 9 | ||
| 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 8 | ||
| 998 | |g 124458912 |a Veltmann, Christian |m 124458912:Veltmann, Christian |d 60000 |d 61000 |e 60000PV124458912 |e 61000PV124458912 |k 0/60000/ |k 1/60000/61000/ |p 7 | ||
| 999 | |a KXP-PPN1850471088 |e 4339904392 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"eki":["1850471088"],"doi":["10.1139/Y10-094"]},"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"pubHistory":["42.1964 -"],"recId":"320436047","id":{"zdb":["2004356-9"],"eki":["320436047"],"issn":["1205-7541"]},"disp":"Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2Canadian journal of physiology and pharmacology","titleTranslated":[{"translated":"Revue canadienne de physiologie et pharmacologie"}],"origin":[{"dateIssuedKey":"1964","publisher":"NRC Research Press","dateIssuedDisp":"1964-","publisherPlace":"Ottawa, Ont."}],"note":["Gesehen am 13.04.2022","Fortsetzung der Druck-Ausgabe"],"type":{"media":"Online-Ressource","bibl":"periodical"},"title":[{"title_sort":"Canadian journal of physiology and pharmacology","subtitle":" = Revue canadienne de physiologie et pharmacologie","title":"Canadian journal of physiology and pharmacology"}],"part":{"issue":"12","text":"88(2010), 12, Seite 1181-1190","pages":"1181-1190","year":"2010","volume":"88","extent":"10"},"language":["eng","fre"]}],"physDesc":[{"extent":"10 S."}],"name":{"displayForm":["Jonathan M. Cordeiro, Guillermo J. Perez, Nicole Schmitt, Ryan Pfeiffer, Vladislav V. Nesterenko, Elena Burashnikov, Christian Veltmann, Martin Borggrefe, Christian Wolpert, Rainer Schimpf, Charles Antzelevitch"]},"recId":"1850471088","origin":[{"dateIssuedKey":"2010","dateIssuedDisp":"1 December 2010"}],"note":["Gesehen am 16.06.2023"],"title":[{"title_sort":"Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2","title":"Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"person":[{"role":"aut","given":"Jonathan M.","family":"Cordeiro","display":"Cordeiro, Jonathan M."},{"role":"aut","given":"Guillermo J.","display":"Perez, Guillermo J.","family":"Perez"},{"given":"Nicole","role":"aut","family":"Schmitt","display":"Schmitt, Nicole"},{"role":"aut","given":"Ryan","display":"Pfeiffer, Ryan","family":"Pfeiffer"},{"given":"Vladislav V.","role":"aut","family":"Nesterenko","display":"Nesterenko, Vladislav V."},{"display":"Burashnikov, Elena","family":"Burashnikov","role":"aut","given":"Elena"},{"family":"Veltmann","display":"Veltmann, Christian","given":"Christian","role":"aut"},{"given":"Martin","role":"aut","family":"Borggrefe","display":"Borggrefe, Martin"},{"given":"Christian","role":"aut","family":"Wolpert","display":"Wolpert, Christian"},{"given":"Rainer","role":"aut","family":"Schimpf","display":"Schimpf, Rainer"},{"role":"aut","given":"Charles","family":"Antzelevitch","display":"Antzelevitch, Charles"}]} | ||
| SRT | |a CORDEIROJOOVERLAPPIN1201 | ||