(1,4) Congenital factors include mutations in the human cardiac ether-a-go-go-related gene (HERG) and the MinK-related peptide 1 (MiRP1
) gene, which encode ion channel proteins.
The [I.sub.Kr] current is conducted through an ion channel most likely composed of four HERG subunits (3) in combination with an unknown number of MiRP1 subunits (4).
The remainder may have mutations in KCNE1 or KCNE2 encoding minx (8) and MiRP1 (4), respectively, or in the SCN5A gene encoding the SCN5A [Na.sup.+]-ion channel conducting the [I.sub.Na] current responsible for the initial depolarization of the action potential (9,10).
Thus, in agreement with the previous study, our data suggest that the direct involvement of MiRP1 in LQTS is rare.
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.
More recently, Abbott et al identified MiRP1 as a [Beta]-subunit for HERG (see "LQT6: MiRP1").
MiRP1, the minK-related peptide 1, or KCNE2, is a novel potassium channel gene recently cloned and characterized by Abbott and colleagues. MiRP1 is a 123-amino-acid channel protein with a single predicted transmembrane segment similar to that described for minK. Chromosomal localization studies mapped this KCNE2 gene to chromosome 21q22.1 (Figure 2), within 79 kb of KCNE1 (minK) and arrayed in opposite orientation. The open reading frames of these 2 genes share 34% identity, and both are contained in a single exon, suggesting that they are related through gene duplication and divergent evolution.
These similar channel proteins (ie, minK and MiRP1) suggest that a family of channels exist that regulate ion channel [Alpha]-subunits.