The KCNE1 gene has been associated with autosomal recessive Jervell and Lange-Nielsen Syndrome (JLNS) in 4 probands in 11 publications. At least 4 unique variants (missense, in-frame indel) have been reported in humans, and variants in this gene segregated with disease in 4 additional family members. KCNE1 was first associated with this disease in humans in 1997 (Tyson et al.). The mechanism for disease is homozygous loss of function causes irregular myocyte polarization from K+ channel activity leading to LQT and inner ear malformations causing HL and vestibular dysfunction (PMID: 9354783). This gene-disease association is supported by animal models, expression studies and in vitro functional assays showing the potential of variation in the protein to cause irregular heart conductivity and hearing loss. It is important to note that the KCNQ1 gene comprises a large percentage of the JLNS cases currently published in the literature and that though this appears to be a largely accepted gene-disease association, there is not quite enough case level information to reach a Definitive classification. However there is a large amount of experimental evidence showing the interaction between KCNE1 and KCNQ1 though this information was not scored. In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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