Remarkably, three unrelated families harbor pathogenic variations affecting the corresponding Arg73 residue in the related TMEM216 protein, also associated with JS (Arg73Leu, Arg73His and Arg 73Cys) and MKS (Arg73His) [35] (S1 Supplementary Figure 1). This evidence concerns the gene TMEM216 and Meckel syndrome, type 1.