Retinitis pigmentosa and related disorders: Phenotypes of rhodopsin and peripherin/RDS mutations

Abstract

Retinitis pigmentosa comprises a group of clinically variable and genetically heterogeneous inherited disorders of the retina. It is estimated that approximately 1.5 million people throughout the world are affected by this disease. It is a slowly progressive disorder and causes loss of night vision and peripheral visual field in adolescence. It can be inherited through an autosomal dominant, recessive, or X-linked mode; the autosomal dominant form is considered to be the mildest form. Molecular genetic studies on the autosomal dominant disorder have shown that, in some families, genes encoding the rhodopsin and peripherin/RDS map very close to the disease loci identified previously by the systematic linkage analyses. These results, together with the observation that a recessive nonsense mutation in the Drosophila opsin gene causes photoreceptor degeneration, prompted an extensive search for the alterations in the human rhodopsin and peripherin/RDS genes in families with autosomal dominant retinitis pigmentosa. As a result, several distinct rhodopsin and peripherin/RDS mutations have been found in approximately 30% of all autosomal dominant cases. A wide variety of clinical expression of the disorder even within a family with the same mutation, its late onset, slow progression, and cone degeneration clearly suggest that some other factors or genes in addition to rhodopsin are responsible for the phenotypic expression of the disorder. In this article, an attempt is made to highlight some of these recent developments and to correlate the various mutations and the phenotypes.

Molecular Cloning, Expression, and Characterization of a Novel Human Serine/Threonine Protein Phosphatase, PP7, That Is Homologous toDrosophila Retinal Degeneration C Gene Product (rdgC)

“…Mutations in either rdgA or rdgB result in retinal degeneration. This is similar to the effect of mutations in genes encoding key components of mammalian phototransduction (46,47). Furthermore, in Drosophila the rdgB mutant phenotype can be rescued by the expression of a mammalian homologue, MrdgB (48).…”

Chemical Kinetic Analysis of Thermal Decay of Rhodopsin Reveals Unusual Energetics of Thermal Isomerization and Hydrolysis of Schiff Base

“…Our model can be used to reveal the possible cause of eye diseases such as retinitis pigmentosa (RP), a family of inherited visual disorders characterized by progressive degeneration of the retina and retinal pigment epithelium (42)(43)(44)(45)(46)(47). Approximately 25% of autosomal dominant RP cases are known to connect to one of over 100 point mutations in the rhodopsin gene, whereas additional rhodopsin mutations account for some cases of autosomal recessive RP and congenital stationary night blindness (48,49).…”

The genotype‐phenotype controversy in ophthalmology, Implications of heterogeneity on diagnosis, embryology and molecular function

“…This may of course eventually induce many successive steps but presumably within the embryological pathway of that specific tissue. Thus when a gene product of a mutation, like RDS/peripherin, results in either macular dystrophy or peripheral retinal disease (Weleber et al 1993, Shastry 1994, Kohl et al 1996, the wild type gene product is presumably an important element in the differentiation of both rods and cones.…”

“…Similar examples of genetic heterogeneity and clinical similarity are cyclopia, optic atrophy, retinitis pigmentosa (Shastry 1994, McKusick 1994, Rieger syndrome(s) (Legius et al 1994; Walter et al 1996) and many others. In these cases, geneticists are splitters, clinicians are lumpers.…”