The LQT1 locus (KCNQ1) has been correlated with the most common form of 
inherited long QT (LQT) syndrome. LQT patients suffer from syncopal episodes and 
high risk of sudden death. The KCNQ1 gene encodes KvLQT1 alpha-subunits, which 
together with auxiliary IsK (KCNE1, minK) subunits form IK(s) K(+) channels. 
Mutant KvLQT1 subunits may be associated either with an autosomal dominant form 
of inherited LQT, Romano-Ward syndrome, or an autosomal recessive form, Jervell 
and Lange-Nielsen syndrome (JLNS). We have identified a small domain between 
residues 589 and 620 in the KvLQT1 C-terminus, which may function as an assembly 
domain for KvLQT1 subunits. KvLQT1 C-termini do not assemble and KvLQT1 subunits 
do not express functional K(+) channels without this domain. We showed that a 
JLN deletion-insertion mutation at KvLQT1 residue 544 eliminates important parts 
of the C-terminal assembly domain. Therefore, JLN mutants may be defective in 
KvLQT1 subunit assembly. The results provide a molecular basis for the clinical 
observation that heterozygous JLN carriers show slight cardiac dysfunctions and 
that the severe JLNS phenotype is characterized by the absence of KvLQT1 
channel.