Polymorphic variation within “conserved” sequences at the 3′ end of the human RDS gene which results in amino acid substitutions

Abstract

The human RDS gene, previously mapped to chromosome 6p, encodes a protein found in the outer disc membrane of the photoreceptor cells of the retina. The cDNA sequence of the human gene shows 85% identity with the bovine peripherin gene and the rds (retinal degeneration slow) genes from mouse and rat. Mutations in the RDS gene have recently been implicated in autosomal dominant retinitis pigmentosa (adRP) in some families. Here we present evidence that the third exon of this gene is subject to polymorphic variation in humans. The three sequence alterations described in this paper give rise to amino acid substitutions. However, as these missense mutations also occur in the normal population they are not implicated as causing adRP. Interestingly such sequence variation is not found within other species examined including mouse and bovine. These intragenic polymorphisms will be of future potential value in studies to locate further disease causing mutations in adRP patients in the RDS gene.

A heterozygous novel C253Y mutation in the highly conserved cysteine residues of ROM1 gene is the cause of retinitis pigmentosa in a Spanish family?

“…Thus, DGGE analysis and direct sequence of peripherin/RDS gene was carried out. No sequence variation was detected in peripherin/RDS gene, except for the previously reported polymorphisms in exon 3 (Jordan et al, 1992). Co-segregation of such polymorphisms together with the mutation C253Y in the family (not show) excluded a possible digenic mechanism between peripherin/RDS and ROM1 gene.…”

Adult vitelliform macular dystrophy is frequently associated with mutations in the peripherin/RDS gene

“…The C 1054 > T polymorphism was verified by restriction enzyme digestion using HaeIII and resulted in a frequency of 0.71/0.29 (wild-type/mutant) in our patient sample and in a frequency of 0.77/0.23 (wild-type/mutant) in the controls (Table 3). The K310R amino acid polymorphism previously described by Jordan et al (1992) was not detected by SSCA under the conditions used in our laboratory. To assess the frequency of this polymorphism, we analyzed an MboII polymorphism underlying the K310R variation; 24 of 28 AVMD patients were ho- was identified on a rare C 1054 T/E304Q/G338D haplotype (closed triangle).…”

Three novel RDS-peripherin mutations (689delT, 857del17, G208D) in Spanish familes affected with autosomal dominant retinal degenerations

“…This aminoacid takes place in the second intradiscal loop and is highly conserved in many other species like rat, mouse and bovine (Jordan et al, 1992). In our case the neutral aminoacid glycine is replaced by an aminoacid with a negatively charged radical group aspartic, hence the mutation probably alters the secondary structure of the protein.…”