A Novel Mutation (Asn244Lys) in the Peripherin/RDS Gene Causing Autosomal Dominant Retinitis Pigmentosa Associated with Bull's-Eye Maculopathy Detected by Nonradioisotopic SSCP

Kikawa, Emi; Nakazawa, Makoto; Chida, Yasushi; Shiono, Takashi; Tamai, Makoto

doi:10.1006/geno.1994.1142

Cited by 42 publications

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“…It is a glycoprotein of 39 kDa (346 amino acids), is highly conserved among mice, cattle, rats and humans and is thought to play an important role in the assembly, orientation and physical stability of the membranous disc of rods and cones. Mutations in the human peripherin/RDS gene have been found (table 3) in families with RP [44,[112][113][114][115][116][117][118][119][120], butterfly shaped pigment dystrophy [121][122][123], retinitis punctata albescens [124], pattern dystrophy [125], macular dystrophy [126][127][128], fundus flavimaculatus [129], bull's eye maculopathy [130], central areolar choroidal dystrophy [131], and cone-rod dystrophy [132,133]. Thus, mutations in the peripherin/RDS gene are associated with radically different phenotypes.…”

Section: Mutation In the Peripherin/rds Genementioning

confidence: 99%

“…A three base pair (bp) delection of codon 153 or 154 can produce clinically disparate phenotypes even within the same family [129]. Patients with Gly-167-Asp and Asn-224-Lys mutations have widely different clinical phenotypes [121,130,132]. In some families, there is a selective loss of central vision whereas loss of peripheral vision occurs in others.…”

Section: Mutation In the Peripherin/rds Genementioning

confidence: 99%

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Signal transduction in the retina and inherited retinopathies

Shastry

1997

Cellular and Molecular Life Sciences (CMLS)

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In this paper, an attempt is made to highlight some of the recent developments in genetics to understand the group of inherited eye disorders referred to as retinitis pigmentosa (RP). Of the seven genes identified, six are expressed specifically in the photoreceptor cells and four encode the enzymes involved in the phototransduction pathway. A short discussion is presented of the tremendous phenotypic heterogeneity. An understanding of RP requires knowledge of other genetic and environmental factors as well as tests to measure the status of the patient's photoreceptor cells in various disease stages.

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Section: Mutation In the Peripherin/rds Genementioning

confidence: 99%

Section: Mutation In the Peripherin/rds Genementioning

confidence: 99%

Signal transduction in the retina and inherited retinopathies

Shastry

1997

Cellular and Molecular Life Sciences (CMLS)

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1995

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SummaryHeterozygous missense mutation in codon 15 of the rhodopsin gene was detected in a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition of adenine to guanine at the second nucleotide in codon 15 (AAT~AGT), corresponding to a substitution of serine residue for asparagine residue (Asn-15-Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal recessive RP (ARRP) and 34 normal individuals had this alteration. Her funduscopic findings were sectorial in type similar to that of the patients with the same mutation found in an Australian pedigree (Sullivan et al., 1993). This study shows phenotypic similarities in patients with the same mutation of a different ancestry.

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“…R172W and N244H are both associated with macular dystrophy or cone/rod dystrophy (cone‐targeted) , but our results indicate that the secondary structure of the R172W D2 loop is similar to that of the wild‐type D2 loop, while the N244H D2 loop exhibits reduced α–helicity compared to WT. Similarly, the percentage of α–helix in the N244K D2 loop is similar to that of the wild‐type D2 loop, but the percentage in the C214S D2 loop is reduced, even though both cause autosomal dominant retinitis pigmentosa or rod/cone dystrophy . The only other study that has examined the secondary structure of RDS reported very little change in secondary structure in the case of the P216L autosomal dominant retinitis pigmentosa mutation , although that study examined the secondary structure of the entire RDS polypeptide (not just the D2 loop), so it is difficult to compare results.…”

Section: Discussionmentioning

confidence: 97%

Structural characterization of the second intra‐discal loop of the photoreceptor tetraspanin RDS

et al. 2012

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Vertebrate photoreceptors contain a unique tetraspanin protein known as 'retinal degeneration slow' (RDS). Mutations in the RDS gene have been identified in a variety of human retinal degenerative diseases, and more than 70% of these mutations are located in the second intra-discal (D2) loop, highlighting the importance of this region. Here we examined the conformational and thermal stability properties of the D2 loop of RDS, as well as interactions with ROM-1, a non-glycosylated homolog of RDS. The RDS D2 loop was expressed in Escherichia coli as a fusion protein with maltose binding protein (MBP). The fusion protein, referred to as MBP-D2, was purified to homogeneity. Circular dichroism spectroscopy showed that the wild-type (WT) D2 loop consists of approximately 21% a-helix, approximately 20% b-sheet and approximately 59% random coil. D2 loop fusion proteins carrying disease-causing mutations in RDS (e.g. R172W, C214S, N244H/K) were also examined, and conformational changes were observed (compared to wild-type D2). In particular, the C150S, C214S and N244H proteins showed significant reductions in a-helicity. However, the thermal stability of the mutants was unchanged compared to wild-type, and all the mutants were capable of interacting with ROM-1, indicating that this functional aspect of the isolated D2 loop remained intact in the mutants despite the observed conformational changes. An I-TASSER model of the RDS D2 loop predicted a structure consistent with the circular dichroism experiments and the structure of the conserved region of the D2 loop of other tetraspanin family members. These results provide significant insight into the mechanism of RDS complex formation and the disease process underlying RDS-associated retinal degeneration.

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A Novel Mutation (Asn244Lys) in the Peripherin/RDS Gene Causing Autosomal Dominant Retinitis Pigmentosa Associated with Bull's-Eye Maculopathy Detected by Nonradioisotopic SSCP

Cited by 42 publications

References 0 publications

Signal transduction in the retina and inherited retinopathies

Signal transduction in the retina and inherited retinopathies

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

Structural characterization of the second intra‐discal loop of the photoreceptor tetraspanin RDS

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