Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13)

Lith-Verhoeven, Janneke J.C. van; Velde-Visser, S.D. van der; Sohocki, Melanie M.; Deutman, August F.; Brink, H.; Cremers, F.P.M.; Hoyng, C.B.

doi:10.1076/opge.23.1.1.2206

Cited by 24 publications

(21 citation statements)

References 37 publications

(35 reference statements)

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“…Four papers (Kondo, et al, 2003;MartinezGimeno, et al, 2003;van Lith-Verhoeven, et al, 2002;Walia, et al, 2008) provide more detailed descriptions of the phenotype associated with individual mutations but give at best only a limited comparison with clinical findings in other families. Here we present clinical data on a family and two cases with new mutations, a de novo case of a known mutation, additional clinical data on two published families, and an overview of previously published clinical findings in eight further families.…”

Section: Discussionmentioning

confidence: 99%

“…Legend: NR= non-recordable; VA= visual acuity; CMO= central macular oedema; CF= counting fingers; HM= hand movements; PSCLO= posterior subcapsular lens opacity; PSCC= posterior subcapsular cortical cataract. References; Dutch family (van Lith-Verhoeven, et al, 2002), British 1 (McKie, et al, 2001;, British 2 (described herein), South African (Greenberg, et al, 1994;McKie, et al, 2001), US1 (Walia, et al, 2008), Japanese (Kondo, et al, 2003), Spanish 1-4 (Martinez-Gimeno, et al, 2003), British 3, 4 and 5 (described herein) and US2 (Kojis, et al, 1996). frame-shift 2325fsX2359 (Kondo, et al, 2003) c.6991delG frame-shift E2331fsX2358 (Sullivan, et al, 2006) IVS exon 41/ 42 junction IVS41-4G>A Splice site change (Sullivan, et al, 2006) -Gimeno, et al, 2003) Nucleotide numbering reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence (accession number NG_009118), according to journal guidelines (www.hgvs.org/mutnomen).…”

Section: Genotype-phenotype Analysismentioning

confidence: 99%

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Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes

et al. 2010

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PRPF8-retinitis pigmentosa is said to be severe but there has been no overview of phenotype across different mutations. We screened RP patients for PRPF8 mutations and identified three new missense mutations, including the first documented mutation outside exon 42 and the first de novo mutation. This brings the known RP-causing mutations in PRPF8 to nineteen. We then collated clinical data from new and published cases to determine an accurate prognosis for PRPF8-RP. Clinical data for 75 PRPF8-RP patients were compared, revealing that while the effect on peripheral retinal function is severe, patients generally retain good visual acuity in at least one eye until the fifth or sixth decade. We also noted that prognosis for PRPF8-RP differs with different mutations, with p.H2309P or p.H2309R having a worse prognosis than p.R2310K. This correlates with the observed difference in growth defect severity in yeast lines carrying the equivalent mutations, though such correlation remains tentative given the limited number of mutations for which information is available. The yeast phenotype is caused by lack of mature spliceosomes in the nucleus, leading to reduced RNA splicing function. Correlation between yeast and human phenotypes suggests that splicing factor RP may also result from an underlying splicing deficit.

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Section: Discussionmentioning

confidence: 99%

Section: Genotype-phenotype Analysismentioning

confidence: 99%

Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes

et al. 2010

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“…retina. A severe form of this disease (RP13) was found to be associated with mutations in human PRP8 (McKie et al 2001;De Erkenez et al 2002;van Lith-Verhoeven et al 2002;Kondo et al 2003;Martinez-Gimeno et al 2003). The association of hPrp8p with a retinal-specific disorder was a surprising result, as Prp8 function is required in all cell types.…”

Section: Mpn (Mpr-1 Pad-1 N-terminal) Domainmentioning

confidence: 99%

Prp8 protein: At the heart of the spliceosome

Grainger¹,

Beggs²

2005

RNA

321

386

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Pre-messenger RNA (pre-mRNA) splicing is a central step in gene expression. Lying between transcription and protein synthesis, pre-mRNA splicing removes sequences (introns) that would otherwise disrupt the coding potential of intron-containing transcripts. This process takes place in the nucleus, catalyzed by a large RNA-protein complex called the spliceosome. Prp8p, one of the largest and most highly conserved of nuclear proteins, occupies a central position in the catalytic core of the spliceosome, and has been implicated in several crucial molecular rearrangements that occur there. Recently, Prp8p has also come under the spotlight for its role in the inherited human disease, Retinitis Pigmentosa.Prp8 is unique, having no obvious homology to other proteins; however, using bioinformatical analysis we reveal the presence of a conserved RNA recognition motif (RRM), an MPN/JAB domain and a putative nuclear localization signal (NLS). Here, we review biochemical and genetical data, mostly related to the human and yeast proteins, that describe Prp8's central role within the spliceosome and its molecular interactions during spliceosome formation, as splicing proceeds, and in post-splicing complexes. NOTE ON NOMENCLATUREIn this review, Prp8 and Prp8p represent the protein product of the wild-type PRP8 gene of Saccharomyces cerevisiae, while prp8-1 is an example of a mutant allele of the PRP8 gene. Human Prp8 protein is designated hPrp8, also known in the literature as PRPF8, PRPC8, p220, and 220K. In some places, to avoid confusion, yPrp8 is used to distinguish the yeast (S. cerevisiae) protein from the human form. sPrp8 SPP42 (Schmidt et al. 1999) or sPrp8 cwf6 (McDonald et al. 1999;Ohi et al. 2002) defines the ortholog in Schizosaccharomyces pombe. Confusingly, the cdc28 gene in S. pombe is also referred to as prp8 as a consequence of its role in both pre-mRNA splicing and cell cycle progression, and there is also a temperature-sensitive allele called prp8-1 that causes accumulation of pre-mRNA upon a shift to nonpermissive temperatures (Lundgren et al. 1996;Imamura et al. 1998). Cdc28 prp8 encodes a 112-kDa DEAH-box protein. This protein is not the ortholog of the U5 snRNP protein of S. cerevisiae that is discussed here.In discussions of pre-mRNA-protein cross-links or mutations that affect intron-exon junctions, 5ЈSS+2 refers to the second intronic base from the 5Ј end of the intron, 5ЈSS-2 is the penultimate base of the 5Ј exon, and 3ЈSS-2 is the penultimate base of the intron. PRE-mRNA SPLICINGPre-mRNA splicing involves two trans-esterification reactions within the highly dynamic spliceosome complex. A vast amount of mainly biochemical data led to a consensus view of an ordered pathway of spliceosome assembly that will be described in outline here (for further details, see Kramer 1996;Burge et al. 1999;Brow 2002). The small nuclear RNA-protein (snRNP) complexes, known as U1, U2, U4, U5, and U6 snRNPs, play key roles. U1 is the first snRNP to associate with pre-mRNA, interacting with the 5Ј splice site (5Ј...

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“…Although most adRP genes are expressed predominantly in the retina, three genes have been identified that are ubiquitously expressed in different tissues. These non-retina-specific adRP genes encode proteins essential for pre-mRNA splicing, including HPRP3 [for RP18 (Anthony et al, 1997;Chakarova et al, 2002)], PRPC8 [for RP13 (McKie et al, 2001;van Lith-Verhoeven et al, 2002)], and PRPF31 [for RP11 (Moore et al, 1993;Evans et al, 1995;Al-Maghtheh et al, 1996;Vithana et al, 2001)]. In fact, RP11 has been reported as the second most common locus for adRP (Vithana et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Mutations in PRPF31 Inhibit Pre-mRNA Splicing of Rhodopsin Gene and Cause Apoptosis of Retinal Cells

Lu¹,

Kawada²,

Havlioglu³

et al. 2005

J. Neurosci.

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Mutations in human PRPF31 gene have been identified in patients with autosomal dominant retinitis pigmentosa (adRP). To begin to understand mechanisms by which defects in this general splicing factor cause retinal degeneration, we examined the relationship between PRPF31 and pre-mRNA splicing of photoreceptor-specific genes. We used a specific anti-PRPF31 antibody to immunoprecipitate splicing complexes from retinal cells and identified the transcript of rhodopsin gene (RHO) among RNA species associated with PRPF31-containing complexes. Mutant PRPF31 proteins significantly inhibited pre-mRNA splicing of intron 3 in RHO gene. In primary retinal cell cultures, expression of the mutant PRPF31 proteins reduced rhodopsin expression and caused apoptosis of rhodopsinpositive retinal cells. This primary retinal culture assay provides an in vitro model to study photoreceptor cell death caused by PRPF31 mutations. Our results demonstrate that mutations in PRPF31 gene affect RHO pre-mRNA splicing and reveal a link between PRPF31 and RHO, two major adRP genes.

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Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13)

Cited by 24 publications

References 37 publications

Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes

Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes

Prp8 protein: At the heart of the spliceosome

Mutations in PRPF31 Inhibit Pre-mRNA Splicing of Rhodopsin Gene and Cause Apoptosis of Retinal Cells

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