GJA12/GJC2 mutations associated with CNS diseases. This is a schematic drawing of human Cx47, illustrating the position and nature of mutations associated with CNS diseases. I33M (grey circle) is located in the first transmembrane domain. All of the other mutations depicted cause PMLD (black circles), either as homozygous mutations or as compound heterozygote mutations (missense mutations: P87S, G146S, G233R, G233S, T262A, Y269D, M283T and T395I; frameshift mutations: L25fs, P128fs, E204fs, L278fs, P302fs, C315fs, A322fs and P327fs; non-sense mutations: Y229stop and R237stop; complex mutations: A95G____V96insertT) (Uhlenberg et al., 2004; Bugiani et al., 2006; Salviati et al., 2007; Wolf et al., 2007; Henneke et al., 2008). The positions of the transmembrane domains are based on the work of Yeager and Nicholson (Yeager and Nicholson, 1996).