two of which affected the same amino acid codon, and one was a 1-bp indel that is predicted to cause a frameshift and a termination codon seven amino acids downstream. One mutation, c1036T, was shared between two unrelated individuals with Miller syndrome who are of different self-identified geographical ancestry. Each of the amino acid residues affected by a DHODH mutation is highly conserved among homologues studied to date (Supplementary Figure 1). A single validated nonsynonymous polymorphism in human DHODH has been studied by Grabar et al.19 This polymorphism causes a lysine to glutamine substitution in the relatively diverse N-terminal extension of dihydroorotate dehydrogenase that is responsible for the association of the enzyme with the inner mitochondrial membrane.
