CLCN1 and Dyggve-Melchior-Clausen disease: Dominant CLCN1 variants in DMC patients have a dominant negative effect (the negative impact of the mutated subunit on the co-expressed wild-type subunit) that causes a large shift in gating potential and prevents the ClC-1 channels from opening when required in repolarization, increasing the excitability of the membrane, manifested as myotonia (12).