Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa

Abstract

The murine retinal degeneration slow (rds) gene is a semidominant mutation with a phenotype having rod and cone photoreceptors that develop abnormally and then slowly degenerate. The phenotype is a possible model for retinitis pigmentosa, one of the scores of hereditary human retinal degenerations, which is also characterized by photoreceptor degeneration. We report here three mutations of the human homologue of the rds gene (RDS) that cosegregate with autosomal dominant retinitis pigmentosa in separate families. Our results indicate that some cases of autosomal dominant retinitis pigmentosa are due to mutations at the RDS locus.

Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP)

“…Almost 30~ in ADRP patients have one of these mutations in the United States . On the other hand~ it was found that the mutations of peripherin-RDS (retinal degenera-tion slow: 6p12) gene locus cosegregate with ADRP in separate families (Farrar et al, 1991 ;Kajiwara et al, 1991). These facts indicate that some cases of ADRP are due to not only the mutation at rhodopsin gene locus but also at peripherin-RDS gene locus.…”

Differences in RDS trafficking, assembly and function in cones versus rods: insights from studies of C150S-RDS

“…In contrast, we have reported that cones lacking RDS (in the cone-dominant neural retina leucine zipper knockout, nrl 2/2 , background) (7 -9) retain some OS function and structure, albeit abnormal (3,10). This divergence in the role of RDS in rods versus cones is underscored by the observation that mutations in the human Rds gene are associated with a variety of rod-or conedominant blinding retinal diseases, including autosomal dominant retinitis pigmentosa and multiple classes of macular degeneration (11,12). The large variety and severity in RDS-related disease make evaluation of its role in OS biogenesis key to our understanding of photoreceptor cell biology and to the development of rational treatments for multiple forms of retinal degeneration.…”

Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant retinitis pigmentosa

“…Mutations in rhodopsin gene Sung et al, 1991a;Inglehearn et al, 1992;Macke et al, 1993), peripherin/RDS gene (Farrar et al, 1991;Kajiwara et al, 1991) and other candidate genes have been found in patients with RP. In Japan, three families with Thr-17-Met , Glu-181-Lys (Saga et al, 1994), or Pro-347-Leu mutation in the rhodopsin gene, and two families with Cys-214-Ser (Saga et al, 1993) or Asn-244-Lys mutation (Kikawa et al, 1994) in the peripherin/RDS gene have been reported as autosomal dominant RP (ADRP).…”