Connexion

GENATLAS PHENOTYPE

last update : 28-03-2009

Symbol	LQT1
Location	11p15.5
Name	long QT syndrome with ventricular tachyarrhythmia, type 1
Other name(s)	Romano-Ward syndrome
Corresponding gene	KCNQ1
related resource	LongQTSyndromeDatabase
Other symbol(s)	LQT, RWS
Main clinical features	characterized by syncopes, seizures predisposing to torsades de pointes and ventricular fibrillation, accounting for 50p100 of cases of the Romano-Ward syndrome, potentially decreasing the outward K+ currents, leading to a high level of membrane depolarization associated with compound heterozygosity for two mutations of KCNQ1
Genetic determination	autosomal recessive
	autosomal dominant
Function/system disorder	cardiovascular
Type	disease

Gene product

Name

cardiac potassium channel (KCNQ1)

Mechanism(s)

Gene mutation	Effect	Comments

various types		mostly dominant negative mutations, with codons 341 and 344 being the hotspots for mutations, mutant retained in the endoplasmic reticulum and unable to translocate to the plasma membrane
missense	abnormal protein/gain of function	P343S, showed a dominant-negative effect on native IKs currents leading to prolongation of the heart repolarisation
missense	haploinsufficiency	M250R, leads to ER-retention and dysfunctional trafficking of the mutant channel resulting in haploinsufficiency
missense	other	G314S exerts a dominant negative effect on expression of KCNQ1 channels in oocytes (Li 2009)

Remark(s)

. F275S KCNQ1 mutation, located within the S5 transmembrane domain, leads to impaired polypeptide trafficking that in turn leads to reduction of channel ion currents and altered gating kinetics (Li 2009)

delV595 and P631fs/19 mutations were found to cause trafficking defects via different mechanisms, impaired complex formation and retention to ER, respectively (Sato 2009)

Genotype/Phenotype correlations

(P343S) increases the risk of malign arrhythmias with sudden cardiac death