RDH12 mutations were first reported simultaneously in several west Austrian families [58], possibly as a founder mutation, and in a significant subset (4.1%) of unrelated LCA patients in France [101] (http://www.retina-international.org/ sci-news/rdhi2mut.htm). RDH12 maps close to the LCA3 locus [126] on i4q24.i, though whilst the linkage analysis performed gave a significant lod score at this locus (3.24-3.87) a maximum lod score of 13.29 was obtained 10 Mb distally. It remains to be seen whether the families mapped to the LCA3 locus have RDH12 mutations or whether there is another LCA gene in the same region.

RDH12 is a photoreceptor-specific gene involved in the production of 11-cis retinal from 11-czs retinol during regeneration of the cone visual pigments [45], though it has dual substrate specificity for both the -cis and -trans retinoids. Whether it is the decrease in 11-cis synthesis and/or accumulation of the all-trans retinal within the photoreceptors that causes the severe LCA phenotype is not yet known.

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