Figure 1.

DHDDS Harbors a Mutation Causing RP

(A) Pedigree of the studied family with three affected offspring indicating a recessive trait.

(B) Three-dimensional structural model of DHDDS indicates an important role for Arg38 in the organization of the enzyme active site. The Lys42Glu mutant allele, being negatively charged, will likely ion pair with the positively charged Arg38 and, in so doing, may lead to distortion of the active site and compromise the binding of farnesyl-pyrophosphate (arrow). A detailed description of the mechanism is provided in Figure S2.

(C) Sanger sequencing confirmed the identified mutation and revealed complete cosegregation with the phenotype.

(D) Lys42 (red box) is a highly conserved residue in multiple species and is located close to the active site of the protein (orange box), indicating strong evolutionary constraints.