Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel: Implications for acquired and congenital long Q-T syndrome

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Standard

Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel : Implications for acquired and congenital long Q-T syndrome. / Larsen, L. A.; Andersen, P. S.; Kanters, J.; Svendsen, I. H.; Jacobsen, J. R.; Vuust, J.; Wettrell, G.; TranebjÆrg, L.; Bathen, J.; Christiansen, M.

I: Clinical Chemistry, Bind 47, Nr. 8, 06.08.2001, s. 1390-1395.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Larsen, LA, Andersen, PS, Kanters, J, Svendsen, IH, Jacobsen, JR, Vuust, J, Wettrell, G, TranebjÆrg, L, Bathen, J & Christiansen, M 2001, 'Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel: Implications for acquired and congenital long Q-T syndrome', Clinical Chemistry, bind 47, nr. 8, s. 1390-1395.

APA

Larsen, L. A., Andersen, P. S., Kanters, J., Svendsen, I. H., Jacobsen, J. R., Vuust, J., Wettrell, G., TranebjÆrg, L., Bathen, J., & Christiansen, M. (2001). Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel: Implications for acquired and congenital long Q-T syndrome. Clinical Chemistry, 47(8), 1390-1395.

Vancouver

Larsen LA, Andersen PS, Kanters J, Svendsen IH, Jacobsen JR, Vuust J o.a. Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel: Implications for acquired and congenital long Q-T syndrome. Clinical Chemistry. 2001 aug. 6;47(8):1390-1395.

Author

Larsen, L. A. ; Andersen, P. S. ; Kanters, J. ; Svendsen, I. H. ; Jacobsen, J. R. ; Vuust, J. ; Wettrell, G. ; TranebjÆrg, L. ; Bathen, J. ; Christiansen, M. / Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel : Implications for acquired and congenital long Q-T syndrome. I: Clinical Chemistry. 2001 ; Bind 47, Nr. 8. s. 1390-1395.

Bibtex

@article{cf260c8e27044a3d8ff97dc9dd3f2197,
title = "Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel: Implications for acquired and congenital long Q-T syndrome",
abstract = "Background: The voltage-gated, rapid-delayed rectifier current (IKr) is important for repolarization of the heart, and mutations in the genes coding for the K+-ion channel conducting this current, i.e., KCNH2 for the α-subunit HERG and KCNE2 for the β-subunit MiRP1, cause acquired and congenital long Q-T syndrome (LQTS) and other cardiac arrhythmias. Methods: We developed a robust single-strand conformation polymorphism-heteroduplex screening analysis, with identical thermocycling conditions for all PCR reactions, covering all of the coding exons in KCNH2 and KCNE2. The method was used to screen 40 unrelated LQTS patients. Results: Eleven mutations, of which six were novel, were found in KCNH2. Interestingly, six mutations were found in the region of the gene coding for the Per-Arnt-Sim (PAS) and PAS-S1 regions of the HERG protein, stressing the need to examine the entire gene when screening for mutations. No mutations were found in KCNE2, suggesting that direct involvement of MiRP1 in LQTS is rare. Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one previously known amino acid polymorphism (T8A) were found in KCNE2. Conclusions: The potential role of rare polymorphisms in the HERG/MiRP1 K+-channel should be clarified with respect to drug interactions and susceptibility to arrhythmia and sudden death.",
author = "Larsen, {L. A.} and Andersen, {P. S.} and J. Kanters and Svendsen, {I. H.} and Jacobsen, {J. R.} and J. Vuust and G. Wettrell and L. Tranebj{\AE}rg and J. Bathen and M. Christiansen",
year = "2001",
month = aug,
day = "6",
language = "English",
volume = "47",
pages = "1390--1395",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry, Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRPI ion channel

T2 - Implications for acquired and congenital long Q-T syndrome

AU - Larsen, L. A.

AU - Andersen, P. S.

AU - Kanters, J.

AU - Svendsen, I. H.

AU - Jacobsen, J. R.

AU - Vuust, J.

AU - Wettrell, G.

AU - TranebjÆrg, L.

AU - Bathen, J.

AU - Christiansen, M.

PY - 2001/8/6

Y1 - 2001/8/6

N2 - Background: The voltage-gated, rapid-delayed rectifier current (IKr) is important for repolarization of the heart, and mutations in the genes coding for the K+-ion channel conducting this current, i.e., KCNH2 for the α-subunit HERG and KCNE2 for the β-subunit MiRP1, cause acquired and congenital long Q-T syndrome (LQTS) and other cardiac arrhythmias. Methods: We developed a robust single-strand conformation polymorphism-heteroduplex screening analysis, with identical thermocycling conditions for all PCR reactions, covering all of the coding exons in KCNH2 and KCNE2. The method was used to screen 40 unrelated LQTS patients. Results: Eleven mutations, of which six were novel, were found in KCNH2. Interestingly, six mutations were found in the region of the gene coding for the Per-Arnt-Sim (PAS) and PAS-S1 regions of the HERG protein, stressing the need to examine the entire gene when screening for mutations. No mutations were found in KCNE2, suggesting that direct involvement of MiRP1 in LQTS is rare. Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one previously known amino acid polymorphism (T8A) were found in KCNE2. Conclusions: The potential role of rare polymorphisms in the HERG/MiRP1 K+-channel should be clarified with respect to drug interactions and susceptibility to arrhythmia and sudden death.

AB - Background: The voltage-gated, rapid-delayed rectifier current (IKr) is important for repolarization of the heart, and mutations in the genes coding for the K+-ion channel conducting this current, i.e., KCNH2 for the α-subunit HERG and KCNE2 for the β-subunit MiRP1, cause acquired and congenital long Q-T syndrome (LQTS) and other cardiac arrhythmias. Methods: We developed a robust single-strand conformation polymorphism-heteroduplex screening analysis, with identical thermocycling conditions for all PCR reactions, covering all of the coding exons in KCNH2 and KCNE2. The method was used to screen 40 unrelated LQTS patients. Results: Eleven mutations, of which six were novel, were found in KCNH2. Interestingly, six mutations were found in the region of the gene coding for the Per-Arnt-Sim (PAS) and PAS-S1 regions of the HERG protein, stressing the need to examine the entire gene when screening for mutations. No mutations were found in KCNE2, suggesting that direct involvement of MiRP1 in LQTS is rare. Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one previously known amino acid polymorphism (T8A) were found in KCNE2. Conclusions: The potential role of rare polymorphisms in the HERG/MiRP1 K+-channel should be clarified with respect to drug interactions and susceptibility to arrhythmia and sudden death.

UR - http://www.scopus.com/inward/record.url?scp=0034911966&partnerID=8YFLogxK

M3 - Journal article

C2 - 11468227

AN - SCOPUS:0034911966

VL - 47

SP - 1390

EP - 1395

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 8

ER -

ID: 204299144