Linkage Validation of <i>RP25</i> Using the 10K GeneChip Array and Further Refinement of the Locus by New Linked Families

Barragán, Isabel; El-Aziz, Mai M. Abd; Borrego, Salud; El-Ashry, Mohamed F.; O'Driscoll, C.; Bhattacharya, Siladitya; Antiñolo, G

doi:10.1111/j.1469-1809.2008.00448.x

Cited by 17 publications

(11 citation statements)

References 33 publications

(45 reference statements)

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“…Other mutations, while rare elsewhere, can be a common cause of arRP in specific populations, such as the RP25 locus which was identified as the genetic cause of 10-20% of arRP cases in Spain [30]. …”

Section: Non-syndromic Retinitis Pigmentosamentioning

confidence: 99%

Retinitis Pigmentosa: Genes and Disease Mechanisms

Parmeggiani

Sorrentino

Ponzin³

et al. 2011

471

239

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Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.

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Section: Non-syndromic Retinitis Pigmentosamentioning

confidence: 99%

Retinitis Pigmentosa: Genes and Disease Mechanisms

Parmeggiani

Sorrentino

Ponzin³

et al. 2011

471

239

View full text Add to dashboard Cite

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“…However, all together the reported loci are responsible for only ∼35-45% of the recessive RP cases, although none of them independently account for a substantial proportion of arRP (more than 10%) [Daiger et al, 2007; Hartong et al, 2006]. In contrast, the RP25 locus, identified by our group in 1998 [Ruiz et al, 1998], was estimated to be linked to 27.7% of Spanish arRP families [Barragán et al, 2008]. Recently, we have identified a new gene encoding an ortholog of Drosophila spacemaker (spam) corresponding to RP25 as a commonly mutated gene in arRP.…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa

et al. 2010

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Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene (EYS) encoding an ortholog of Drosophila spacemaker (spam) as a commonly mutated gene in autosomal recessive RP. In the present study, we report the identification of 73 sequence variations in EYS, of which 28 are novel. Of these, 42.9% (12/28) are very likely pathogenic, 17.9% (5/28) are possibly pathogenic, whereas 39.3% (11/28) are SNPs. In addition, we have detected 3 pathogenic changes previously reported in other populations. We are also presenting the characterisation of EYS homologues in different species, and a detailed analysis of the EYS domains, with the identification of an interesting novel feature: a putative coiled-coil domain. Majority of the mutations in the arRP patients have been found within the domain structures of EYS. The minimum observed prevalence of distinct EYS mutations in our group of patients is of 15.9% (15/94), confirming a major involvement of EYS in the pathogenesis of arRP in the Spanish population. Along with the detection of three recurrent mutations in Caucasian population, our hypothesis of EYS being the first prevalent gene in arRP has been reinforced in the present study. © 2010 Wiley-Liss, Inc.

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“…The high frequency of linkage to RP25 found in the Spanish population (13.7 to 27.7%) and the reproduction of this linkage in families from other parts of the world, suggested RP25 to be a major locus for arRP . Refinement of the genetic interval followed by a bioinformatics based systematic positional cloning approach led to the identification of EYS (NCBI Reference Sequence: NM_001142800.1; MIM# 612424) as the gene responsible for RP25 Barragan et al 2008). Authors reported 6 different mutations in 5 unrelated Spanish families including 4 deletions and 2 nonsense substitutions.…”

Section: Introductionmentioning

confidence: 99%

EYS is a major gene for rod-cone dystrophies in France

et al. 2010

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Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of 239 sporadic and arRP French cases. Direct sequencing of EYS was performed in 186 subjects for whom known mutations had previously been excluded by applying microarray technology. We mostly identified novel mutations in EYS in a total of 29 patients: Fifteen of the mutations were predicted to create premature stop codons and two represent exonic deletions. In addition, twenty missense, silent or splice-site mutations were detected. Patients revealed homozygous or compound heterozygous mutations and in some cases, only a single mutation. Most patients showed classical signs of RP with relatively preserved central vision and visual field until late in the course of the disorder. One patient showed predominance of the disease in the inferior part of the retina suggesting potential phenotypic variability. With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere.

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Linkage Validation of RP25 Using the 10K GeneChip Array and Further Refinement of the Locus by New Linked Families

Cited by 17 publications

References 33 publications

Retinitis Pigmentosa: Genes and Disease Mechanisms

Retinitis Pigmentosa: Genes and Disease Mechanisms

Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa

EYS is a major gene for rod-cone dystrophies in France

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