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==[[Short QT syndrome type 1]] ([[SQT1]])== | ==[[Short QT syndrome type 1]] ([[SQT1]])== | ||
Type 1 SQTS is caused by a mis-sense mutation in KCNH2 gene. It is the most common familial variety of SQTS occurring in autosomal dominant pattern. The KCNH2 gene is located on chromosome 7q 36.1. The KCNH2 gene is often referred as HERG gene. HERG stands for the human ether-a-go-go-related gene which expresses a protein Kv11.1. This protein forms the alpha subunit of potassium channel responsible for rapidly activating rectifier outwards current (Ikr) <ref name="pmid18382206">{{cite journal| author=Schimpf R, Borggrefe M, Wolpert C| title=Clinical and molecular genetics of the short QT syndrome. | journal=Curr Opin Cardiol | year= 2008 | volume= 23 | issue= 3 | pages= 192-8 | pmid=18382206 | doi=10.1097/HCO.0b013e3282fbf756 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18382206 }} </ref>.The genetic analysis reveal mis-sense mutation with cytosine to guanine substitution at nucleotide 1764 resulting in change in the amino acid (N588K) in KCNH2 gene. The N588K mutation appears to be the main reason for occurrence of SQTS syndrome<ref name="pmid19862833">{{cite journal| author=Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA | display-authors=etal| title=The genetic basis of long QT and short QT syndromes: a mutation update. | journal=Hum Mutat | year= 2009 | volume= 30 | issue= 11 | pages= 1486-511 | pmid=19862833 | doi=10.1002/humu.21106 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19862833 }} </ref>. The Bio-physical analysis reveal a gain of function mutation in IKr currents causing shortening of action potential duration and refractoriness making patients prone to re-entrant type of arrythmias <ref name="pmid15828882">{{cite journal| author=Hong K, Bjerregaard P, Gussak I, Brugada R| title=Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. | journal=J Cardiovasc Electrophysiol | year= 2005 | volume= 16 | issue= 4 | pages= 394-6 | pmid=15828882 | doi=10.1046/j.1540-8167.2005.40621.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15828882 }} </ref>. | |||
The N588K mutations cause large outward currents in the ventricles sparing the Purkinje fiber system. The selective shortening of action potentials and shortening of the refractory periods in ventricles and sparing the Purkinje fibers. This differential change promotes residue favorable for reentrant arrhythmia<ref name="pmid16301704">{{cite journal| author=Brugada R, Hong K, Cordeiro JM, Dumaine R| title=Short QT syndrome. | journal=CMAJ | year= 2005 | volume= 173 | issue= 11 | pages= 1349-54 | pmid=16301704 | doi=10.1503/cmaj.050596 | pmc=1283503 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16301704 }} </ref>. | The N588K mutations cause large outward currents in the ventricles sparing the Purkinje fiber system. The selective shortening of action potentials and shortening of the refractory periods in ventricles and sparing the Purkinje fibers. This differential change promotes residue favorable for reentrant arrhythmia<ref name="pmid16301704">{{cite journal| author=Brugada R, Hong K, Cordeiro JM, Dumaine R| title=Short QT syndrome. | journal=CMAJ | year= 2005 | volume= 173 | issue= 11 | pages= 1349-54 | pmid=16301704 | doi=10.1503/cmaj.050596 | pmc=1283503 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16301704 }} </ref>. | ||
Revision as of 17:21, 11 June 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Five variants of short QT syndrome have been characterized based upon the underlying genetic mutation, the electrocardiographic phenotype, and the clinical manifestations of the variant.
Classification
| Type | OMIM | Gene | Gene Location | Mutation | Protein | Notes | |
|---|---|---|---|---|---|---|---|
| 1 | SQTS 1[1][2] | 609620 | KCNH2
HERG[3] |
7q 36.1 | Mutation in the KCNH2 gene causing gain of function of α-subunit Ikr | Kv11.1 | |
| 2 | SQTS 2[1][4] | 609621 | KCNQ1,
KvLQT1[3] |
11p15.5-p15.4 | Mutation in KCNQ1 causing gain of function of α-subunit Iks | Kv7.1 | |
| 3 | SQTS 3[1][5] | 609622 | KCNJ2,
Kir2.1[3] |
17q24.3 | Mutation in KCNJ2 gene causing gain of function of α-subunit IK1 | Kir2.1 | |
| 4 | SQTS 4[1][6] | CACNA1C,
Cav1.2[3] |
12p13.3 | Mutation in CACNB2b causing loss of function of α-subunit IL,Ca | Cav1.2 | ||
| 5 | SQTS 5[1][6] | CACNB2b,
Cavβ2b[3] |
10p12 | Mutation in CACNA1c causing loss of function of β2-subunit IL,Ca | Cavβ2 |
Short QT syndrome type 1 (SQT1)
Type 1 SQTS is caused by a mis-sense mutation in KCNH2 gene. It is the most common familial variety of SQTS occurring in autosomal dominant pattern. The KCNH2 gene is located on chromosome 7q 36.1. The KCNH2 gene is often referred as HERG gene. HERG stands for the human ether-a-go-go-related gene which expresses a protein Kv11.1. This protein forms the alpha subunit of potassium channel responsible for rapidly activating rectifier outwards current (Ikr) [7].The genetic analysis reveal mis-sense mutation with cytosine to guanine substitution at nucleotide 1764 resulting in change in the amino acid (N588K) in KCNH2 gene. The N588K mutation appears to be the main reason for occurrence of SQTS syndrome[1]. The Bio-physical analysis reveal a gain of function mutation in IKr currents causing shortening of action potential duration and refractoriness making patients prone to re-entrant type of arrythmias [8]. The N588K mutations cause large outward currents in the ventricles sparing the Purkinje fiber system. The selective shortening of action potentials and shortening of the refractory periods in ventricles and sparing the Purkinje fibers. This differential change promotes residue favorable for reentrant arrhythmia[9].
Short QT syndrome type 2 (SQT2)
Short QT syndrome type 3 (SQT3)
Short QT syndrome type 4 (SQT4)
Short QT syndrome type 5 (SQT5)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA; et al. (2009). "The genetic basis of long QT and short QT syndromes: a mutation update". Hum Mutat. 30 (11): 1486–511. doi:10.1002/humu.21106. PMID 19862833.
- ↑ Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M; et al. (2004). "Sudden death associated with short-QT syndrome linked to mutations in HERG". Circulation. 109 (1): 30–5. doi:10.1161/01.CIR.0000109482.92774.3A. PMID 14676148.
- ↑ 3.0 3.1 3.2 3.3 3.4 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1161/CIRCEP.109.921056 Check
|pmid=value (help). - ↑ Bellocq C, van Ginneken AC, Bezzina CR, Alders M, Escande D, Mannens MM; et al. (2004). "Mutation in the KCNQ1 gene leading to the short QT-interval syndrome". Circulation. 109 (20): 2394–7. doi:10.1161/01.CIR.0000130409.72142.FE. PMID 15159330.
- ↑ Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A; et al. (2005). "A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene". Circ Res. 96 (7): 800–7. doi:10.1161/01.RES.0000162101.76263.8c. PMID 15761194.
- ↑ 6.0 6.1 Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y; et al. (2007). "Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death". Circulation. 115 (4): 442–9. doi:10.1161/CIRCULATIONAHA.106.668392. PMC 1952683. PMID 17224476.
- ↑ Schimpf R, Borggrefe M, Wolpert C (2008). "Clinical and molecular genetics of the short QT syndrome". Curr Opin Cardiol. 23 (3): 192–8. doi:10.1097/HCO.0b013e3282fbf756. PMID 18382206.
- ↑ Hong K, Bjerregaard P, Gussak I, Brugada R (2005). "Short QT syndrome and atrial fibrillation caused by mutation in KCNH2". J Cardiovasc Electrophysiol. 16 (4): 394–6. doi:10.1046/j.1540-8167.2005.40621.x. PMID 15828882.
- ↑ Brugada R, Hong K, Cordeiro JM, Dumaine R (2005). "Short QT syndrome". CMAJ. 173 (11): 1349–54. doi:10.1503/cmaj.050596. PMC 1283503. PMID 16301704.