Fig. 1. Identification of the OA1 mutations and the pedigrees within the patient collection. A. The OA1 gene structure and the new mutations describe. The exons are shown as open boxes, numbered 1 to 9. The shaded portions of exons 1 and 9 correspond to the 5′ and 3′ UTRs, respectively. Intron sequences are represented by thin lines. The positions of all of the primers used for the mutation analysis are shown (black arrows). The locations and types of mutations identified are shown at the top. B. Direct sequencing of exon 5 of the OA1 gene showing five different mutations as open boxes, including this chromatogram dye terminator sequence traces. Patients #11 and #13 are probands from the same ocular albinism family, patients #7 and #12 are probands of two different families with different origins (from USA and from Germany), patient #3 is a proband of a multigeneration ocular-albinism-affected family from The Netherlands, which shows an additional mutation in exon 6 (see Supplemental Fig. S2). C. Pedigree analyses of a whole family: the solid squares are affected people, the dotted circles are molecularly proven carriers, and hollow squares and circles are unaffected people. The sequence mutation analyses of III #2 probands is also shown. D. Sequence alignment of the OA1 protein between different species: MOUSE, Mus musculus; HUMAN, Homo sapiens; XENTR, Xenopus tropicalis; XENLA, Xenopus laevis; BRARE, Danio rerio; ANOGA, Anopheles gambiae. The arrows show the amino-acid sequence conservation of E185 throughout evolution.

Fig. 2. Confocal microscopy immunofluorescence analyses of the wild-type and mutated Oa1 proteins. Cos-7A cells were transiently transfected with the murine-cDNA-containing vectors expressing wild-type Oa1 (WT) and the 780DelC, and Y311X mutant proteins, as indicated above each set of panels. A. Co-localization (green arrowheads) of the wild-type murine Oa1 tagged with GFP (green; red arrowhead) and H4B4 (red; lysosomal-associated membrane protein). The merged patterns are also shown. B. Different distribution pattern of the Oa1-780DelC murine protein tagged with GFP (green; green arrowheads) and H4B4 (red). The merged patterns are also shown. Yellow arrowheads: partial co-localization of mutant with H4B4. C. Different distribution pattern of the Oa1-W311X murine protein tagged with GFP (green; green arrowhead) and H4B4 (red). The merged patterns are also shown. Yellow arrowheads: partial co-localization of mutant with H4B4. Note different degrees of co-localization of the wild-type Oa1 protein and mutants with the lysosomal-associated H4B4 protein.

New mutations identified in seven out of 18 ocular albinism type 1 patients analysed

Note three new mutations in patient 3 (in blue) and two new mutations in patient 11 (in violet). The patients identified with asterisks are members of the same family.