ALAS2 mutation in the family of patient 1. (A) Pedigree of the CEP family with both ALAS2 and UROS mutations. Cosegregation of UROS mutations (white boxes) and ALAS2 mutations (gray boxes) is shown. (B) Representation of ALAS2 gene: Dark boxes represent untranslated regions and gray boxes coding exons. The red part of the last exon corresponds to the domain in which mutations causing XLDPP have been found (red arrows). The red star corresponds to the Y586F substitution found in the CEP proband (patient 1). (C) C-terminal mutation in ALAS2. Sequence analysis of genomic DNA from CEP patient 1 demonstrating c.1757 A > T (Y586F) mutation in the ALAS2 gene. (D) Comparison of the C-terminal sequence of ALAS enzymes from different species. Red arrows indicate the location of XLDPP mutations and the red star indicates the location of the Y586F substitution.