Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2
and LQT3 forms of congenital long QT syndrome.
LQT1 and LQT2
encode a rectifying potassium channel, while LQT3 encodes the alpha Sodium channel subunit.
Variants in 3 ion channel genes account for over 70% of patients with a definitive diagnosis of LQTS (13, 14) [although the yield is substantially less for all referral cases (15)]: loss of function variants in the potassium ion channel genes potassium voltage-gated channel subfamily Q member 1 (KCNQ1) and potassium voltage-gated channel subfamily H member 2 (KCNH2; LQT1 and LQT2
respectively) and gain of function variants in the sodium ion channel gene sodium voltage-gated channel alpha a subunit 5 (SCN5A; LQT3).
Fukuda, "The generation of induced pluripotent stem cells from a patient with KCNH2 G603D, without LQT2
disease associated symptom," Journal of Medical and Dental Sciences, vol.
Antzelevitch, "Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade de pointes in LQT2
and LQT3 models of the long-QT syndrome," Circulation, vol.
Here, we summarize the current effort to model "electrical human cardiac disease" caused by channelopathies finally leading to LQT-syndromes: LQT1, LQT2
, LQT3, and LQT8 (Table 1).
Ninety percent of the known mutations cause loss of function of ion channels responsible for LQTS types 1 and 2 (LQT1 and LQT2
(6) While mutation in a K+ channel gene HERG or KCNQ2 on chromosome 7 results in LQT2
(about 35-45% of cases).
genotype has arrhythmic events associated with exposure to sudden loud noises (i.e.
Long QT and Jervelle Lange-Nielsen syndromes: Genetic defects and channel abnormalities Syndrome Gene Function Autosomal dominant LQT1 KCNQ1 [I.sub.ks] Decreased LQT2
KCNH2 [I.sub.Kr] Decreased LQT3 SCN5A [I.sub.Na] Decreased LQT4 ANK2 [I.sub.Na, K] Decreased LQT5 KCNE1 [I.sub.ks] Decreased LQT6 KCNE2 [I.sub.kr] Decreased LQT7 KCNJ2 [I.sub.k1] Decreased LQT8 CACNA1C [I.sub.Ca,L] Increased LQT9 CAV3 [I.sub.Na] Increased LQT10 SCN4B [I.sub.Na] Increased Autosomal recessive JLN1 KCNQ1 [I.sub.ks] Decreased JLN2 KCNE1 [I.sub.ks] Decreased Cardiac sodium ([I.sub.Na]), Potassium ([I.sub.ks], [I.sub.Kr], [I.sub.k1]) and Calcium currents
The majority of mutations have been identified in LQT1 (40%-55%), LQT2
(35%-45%), and LQT3 (2%-8%), which represent the genes KCNQ1, KCNH2, and SCN5A, respectively.
The impact of menopause was particularly striking in women with the LQT2