The RDH12 gene encodes an enzyme belonging to a family of dual-specificity retinol dehydrogenases that metabolize both all-trans- and cis-retinols. The RDH12 enzyme is most efficient as an NADPH-dependent retinal reductase with highest activity toward 9-cis and all-trans-retinol. It also helps metabolize short chain aldehydes. The oxido-reductive catalytic activity of the RDH12 enzyme plays an important role in the retinol metabolic process and hence is essential to photoreceptor cell maintenance. Mutations affecting the enzyme activity of RDH12 can thus have pathological consequences.
Mutations in RDH12 are associated with Leber Congenital Amaurosis 13 (LCA13), a severe retinal dystrophy characterized by nystagmus, sluggish pupillary responses, roving eye movement, extreme hyperopia, convergent strabismus, photophobia or keratoconus.
Aldahmesh et al. (2009) carried out a study of 52 non-syndromic Retinitis Pigmentosa (RP) affected patients from 17 Saudi families. DNA obtained from these individuals was used to carry out linkage analysis and homozygosity mapping. Known RP genes in the identified homozygosity blocks were then screened for mutations. The homozygous RDH12 mutation c.226G>C, resulting in the substitution p.G76R, was found to affect three members of a family. The novel missense mutation was not seen in 100 ethnically-matched controls and affected a highly conserved glycine residue.