Long QT Syndrome 5
In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), Paulussen et al. (2004) identified heterozygosity for a 253G-A transition in exon 3 of the KCNE1 gene, previously described by Tesson et al. (1996) as a polymorphism, resulting in an asp85-to-asn (D85N) substitution. Both subjects showed QTc prolongation compared to an electrocardiogram recorded prior to drug exposure (613695). The 85N variant was not found in 32 healthy controls.
In a female patient who had a QTc of 460 ms and suffered cardiac arrest, Westenskow et al. (2004) identified triallelic digenic mutations: homozygosity for D85N in the KCNE1 gene, and heterozygosity for a missense mutation in the KCNH2 gene (152427.0021).
Associations Pending Confirmation
In a study of noise-induced hearing loss susceptibility (NIHL; 613035) in 218 Swedish noise-exposed male workers, Van Laer et al. (2006) genotyped 35 SNPs in 10 candidate genes involved in cell coupling and potassium recycling in the inner ear, and identified the 85N variant of KCNE1 in 5 of 104 noise-susceptible individuals and in none of 114 noise-resistant individuals (p = 0.023). Patch-clamp experiments in Chinese hamster ovary (CHO) cells showed a significant difference in current density and midpoint potential between 85N and wildtype channels. The authors suggested that further studies were necessary before KCNE1 D85N could be designated as a causative SNP.
