LQT2: Difference between revisions
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==LQT2 Subtype== | ==LQT2 Subtype== | ||
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| '''Type''' || '''OMIM''' || '''Mutation''' || '''Notes''' | |||
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| [[LQT2]] || {{OMIM2|152427}} || alpha subunit of the rapid delayed rectifier potassium channel ([[HERG]] + [[MiRP1]]) || Current through this channel is known as I<sub>Kr</sub>. This phenotype is also probably caused by a reduction in repolarizing current. | |||
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The LQT2 type is the second most common [[gene]] location that is affected in long QT syndrome, making up about 35 to 45 percent of all cases. This variant will sometimes come to the attention of the cardiologist as a result of a cardiac event during the post partum period or after being triggered by an alarm clock. This form of long QT syndrome most likely involves mutations of the ''human ether-a-go-go related gene'' ([[HERG]]) on chromosome 7. The [[HERG]] gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (I<sub>Kr</sub>). (The I<sub>Kr</sub> current is mainly responsible for the termination of the [[cardiac action potential]], and therefore the length of the QT interval.) The normally functioning [[HERG]] gene allows protection against early after depolarizations (EADs). | The LQT2 type is the second most common [[gene]] location that is affected in long QT syndrome, making up about 35 to 45 percent of all cases. This variant will sometimes come to the attention of the cardiologist as a result of a cardiac event during the post partum period or after being triggered by an alarm clock. This form of long QT syndrome most likely involves mutations of the ''human ether-a-go-go related gene'' ([[HERG]]) on chromosome 7. The [[HERG]] gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (I<sub>Kr</sub>). (The I<sub>Kr</sub> current is mainly responsible for the termination of the [[cardiac action potential]], and therefore the length of the QT interval.) The normally functioning [[HERG]] gene allows protection against early after depolarizations (EADs). | ||
Revision as of 13:45, 2 October 2012
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Long QT Syndrome Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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LQT2 On the Web |
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American Roentgen Ray Society Images of LQT2 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Overview
LQT2 Subtype
| Type | OMIM | Mutation | Notes |
| LQT2 | 152427 | alpha subunit of the rapid delayed rectifier potassium channel (HERG + MiRP1) | Current through this channel is known as IKr. This phenotype is also probably caused by a reduction in repolarizing current. |
The LQT2 type is the second most common gene location that is affected in long QT syndrome, making up about 35 to 45 percent of all cases. This variant will sometimes come to the attention of the cardiologist as a result of a cardiac event during the post partum period or after being triggered by an alarm clock. This form of long QT syndrome most likely involves mutations of the human ether-a-go-go related gene (HERG) on chromosome 7. The HERG gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (IKr). (The IKr current is mainly responsible for the termination of the cardiac action potential, and therefore the length of the QT interval.) The normally functioning HERG gene allows protection against early after depolarizations (EADs).
There is a possibility, that like in LQT1 mutations, the location of the mutation may have a differing impact on the individual who is affected. A study of 201 patients showed that persons with mutations in the pore region had a greater risk of cardiac events and sudden cardiac death, and that these manifestations occurred earlier than in persons with mutations in the non-pore regions [1].
Most drugs that cause long QT syndrome do so by blocking the IKr current via theHERG gene. These include erythromycin, terfenadine, andketoconazole. The HERG channel is very sensitive to unintended drug binding due to two aromatic amino acids, the tyrosine at position 652 and the phenylalanine at position 656. These amino acid residues are poised so drug binding to them will block the channel from conducting current. Other potassium channels do not have these residues in these positions and are therefore not as prone to blockage.
References
- ↑ Moss AJ, Zareba W, Kaufman ES, Gartman E, Peterson DR, Benhorin J; et al. (2002). "Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel". Circulation. 105 (7): 794–9. PMID 11854117.