The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

The coding regions of KCNE1, KCNE2, KCNE3, KCNE4, and KCNE5 were examined, by direct DNA sequencing, in a cohort of 93 unrelated HCM probands and 188 blood donor controls.Fifteen genetic variants, four previously unknown, were identified in the HCM probands. Eight variants were non-synonymous and one was located in the 3'UTR-region of KCNE4. No disease-causing mutations were found and no significant difference in the frequency of genetic variants was found between HCM probands and controls. Two variants of likely functional significance were found in controls only.Mutations in KCNE genes are not a common cause of HCM and polymorphisms in these genes do not seem to be associated with a propensity to develop arrhythmiaHypertrophic cardiomyopathy (HCM) is a condition characterised by increased wall (predominantly septal) thickness, diastolic dysfunction, and an increased risk of heart failure, stroke and cardiac arrhythmia [1]. The disease has a prevalence of 1:500 in young adults [2], and is considered a hereditary disease caused by mutations in more than 12 genes [3], most of which encode proteins of the sarcomere. The disease exhibits considerable intra-allelic as well as phenotypic heterogeneity. Presently, a genetic aetiology can be identified in 70% of familial cases and 30% of non-familial cases [3].Recently, mutations in genes coding for ion channels have been shown to cause cardiomyopathy. Mutations in SCN5A, coding for the α-subunit of the ion channel conducting the depolarising INa -current [4,5], and in ABCC9 [6], coding for the cardiac specific SUR2A subunit of the KATP potassium channel, have been associated with dilated cardiomyopathy (DCM). The DCM caused by mutations in both SCN5A and ABCC9 is accompanied by cardiac arrhythmia.The KCNE-gene family (KCNE1-5) encodes five small single transmembrane peptides (minK and MiRP1-4, respectively) that function as β-subunits to potassium and pacemaker ion channels [7,8]. The KCNE peptides confer distinctive char