Complexity of phenotype-genotype correlations in Spanish patients with RDH12 mutations

Several mutations have been described in the RDH12 gene that disturb the activity of the encoded protein, suggesting that RDH12 loss of function disrupts the synthetic pathway of the visual chromophore 11-cis-retinal, therefore resulting in early and progressive retinal degeneration (RD). Mutations in this gene have been related to autosomal recessive Leber congenital amaurosis (LCA) and to a form of autosomal recessive childhood-onset severe retinal dystrophy (CSRD). This study was undertaken to attempt to correlate the genotype and phenotype in Spanish CSRD and LCA patients who harbor RDH12 mutations.

A complete ophthalmic and electrophysiologic examination was performed according to preexisting protocols. A screening for mutations was then performed using denaturing HPLC on a DNA fragment analysis system. Those fragments bearing an abnormal pattern were sequenced.

Ten families bearing RDH12 mutations in homozygous or compound heterozygous form were found. All of them corresponded to patients with severe and early-onset retinal dystrophy.

The RDH12-associated phenotype is not homogeneous, the position and nature of the mutations clearly influence the pathologic expression of this disease.