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
Schott et al mapped the fourth LQTS locus to chromosome 4q25-27 (LQT4), while a fifth gene (minK), located on chromosome 21q22,[28,29] was shown to be LQT5. More recently, a sixth gene, the minK-related peptide 1 (MiRP1), localized to 21q22 as well (Figure 2), was identified. Several other families with autosomal-dominant LQTS are not linked to any known LQTS loci, indicating the existence of additional LQTS-causing genes.
Since mutations in KVLQT1 were shown to cause LQTS (LQT1), mutations in minK were sought because mink plays an essential role in the development of [I.sub.Ks] (see "LQT5: minK").