Localization of an autosomal dominant retinitis pigmentosa gene to chromosome 7q

Jordan, Siobhán A.; Farrar, G. Jane; Kenna, Paul F.; Humphries, Marian M.; Sheils, Denise M.; Kumar‐Singh, Rajendra; Sharp, Elizabeth M.; Soriano, N; Ayuso, Carmen; Benı́tez, Javier

doi:10.1038/ng0593-54

Cited by 119 publications

(22 citation statements)

References 29 publications

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“…To date, 14 genes have been identified in individuals with adRP accounting for approximately 50% of all cases (http://www.sph.uth.tmc.edu/RetNet/). The RP10 form has been reported in individuals of American and European (Spanish, Scottish, Irish, and Polish) origin, maps to the long arm of human chromosome 7 (q32.1), [1][2][3][4][5][6][7][8] …”

Section: Conclusion-thementioning

confidence: 99%

Phenotypic Characterization of a Large Family With RP10 Autosomal-Dominant Retinitis Pigmentosa: An Asp226Asn Mutation in the IMPDH1 Gene

Kozma

Hughbanks-Wheaton

Locke

et al. 2005

American Journal of Ophthalmology

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PURPOSE-To evaluate the clinical features associated with the RP10 form of autosomaldominant retinitis pigmentosa in 11 affected members of various ages from one family with a defined IMPDH1 mutation (Asp226Asn). DESIGN-Prospective, observational case series.METHODS-Visual function assessment included visual acuity, color vision, visual field, dark adaptometry, full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Ophthalmologic examinations, fundus photography, and optical coherence tomographic scans were also performed. Blood samples were obtained to screen for basic immune function.RESULTS-Visual acuity was slightly reduced in the teenage years and substantially reduced in association with cystoid macular edema (CME) at all ages. Color defects were observed in three patients (one teen, two adults). Dark-adapted thresholds were elevated. Visual fields were markedly constricted by age 40 (≤20 degrees). Rod and cone a-wave and b-wave ffERG responses were small or nondetectable by age 20, with greater rod than cone loss at all ages. The normal to significantly delayed ffERG cone b-wave implicit times in different patients were explained by their mfERG implicit times from the central retina. The amplification factors (log S) and recovery kinetics derived from the full-field rod a-waves were normal. Optical coherence tomography revealed subretinal fluid accumulation in the majority of eyes. Cystoid macular edema was diagnosed in four patients. No unusual immunologic findings were noted. CONCLUSIONS-TheAsp226Asn mutation is associated with a severe, early-onset form of retinal degeneration in members of this family.Autosomal-dominant retinitis pigmentosa (adRP) is a clinically and genetically heterogenous group of degenerative retinal disorders. To date, 14 genes have been identified in individuals with adRP accounting for approximately 50% of all cases (http://www.sph.uth.tmc.edu/RetNet/). The RP10 form has been reported in individuals of American and European (Spanish, Scottish, Irish, and Polish) origin, maps to the long arm of human chromosome 7 (q32.1), [1][2][3][4][5][6][7][8] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript associates 10 reduced the linkage interval to 3.4 Mb in two unrelated American families and identified a G-to-A transition at codon 226 of the IMPDH1 (inosine-5′-monophosphate dehydrogenase type 1) gene. The resulting Asp226Asn mutation is the most common in the IMPDH1 gene and occurs at a site that is evolutionarily highly conserved, consistent with a highly deleterious consequence of a missense mutation in this region. 10 IMPDH is an enzyme which functions as a homotetramer. IMPDH catalyzes the conversion of inosine monophosphate to xanthine monophosphate, a rate-limiting step in the de novo synthesis of guanine and adenine nucleotides. Xanthine monophosphate is subsequently converted into guanosine di-and triphosphate. There are two vertebrate forms of the enzyme, IMPDH1 and IMPDH2. IMPDH1 expression is believed to be uncha...

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Section: Conclusion-thementioning

confidence: 99%

Phenotypic Characterization of a Large Family With RP10 Autosomal-Dominant Retinitis Pigmentosa: An Asp226Asn Mutation in the IMPDH1 Gene

Kozma

Hughbanks-Wheaton

Locke

et al. 2005

American Journal of Ophthalmology

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“…This heterogeneity is compounded further, as, to date, there are eight known loci for adRP, five for arRP, and four for XlRP (Daiger et al 199S). Jordan et al (1993) reported the localization of one adRP locus, RP10, to chromosome 7q in a Spanish family with a maximum lod (log odds) score of 7.5 at 0% recombination with the microsatellite marker D7S480. A second, independent (American) family linked to 7q was later reported by McGuire et al (199S); this family had a maximum lod score of S.3 at 0% recombination with the more distal marker D7SS14.…”

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confidence: 99%

Mapping the RP10 locus for autosomal dominant retinitis pigmentosa on 7q: refined genetic positioning and localization within a well-defined YAC contig.

et al. 1996

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Retinitis pigmentosa is a genetically heterogeneous disease that has autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP} has thus far been associated with eight distinct loci, including the rhodopsin and peripherin/RDS genes as well as unidentified genes on chromosomes 7p, 7q, 8q, 1710, 17q, and 19q. The RPIO locus for adRP on chromosome 7q was first mapped in a Spanish family; later, an unrelated American family was identified that also showed linkage to 7q. By combining the linkage results from both families, we are able to assign the disease gene to a 5-cM interval on 7q. Based on extensive physical mapping of this region, the genetic interval is now fully contained within a -5-Mb segment on a well-defined YAC contig. These studies significantly reduce the size of the RPIO critical region, exclude a number of possible candidate genes, and provide the necessary cloned DNA for the positional cloning of the RPIO gene.Retinitis pigmentosa (RP) is the name given to a group of degenerative retinal disorders that primarily affect the photoreceptors and retinal pigment epithelium (Heckenlively 1988). A characteristic feature of RP is the bone spicule-like pattern of pigment deposited on the retina, although this deposition is thought to be a consequence and not a cause of the disease. With over 1.5 million people affected worldwide, RP is the most common form of hereditary retinal dysfunction.Clinical characteristics of RP include night blindness and loss of peripheral vision in early adulthood. This is followed by progressive constriction of the mid-and central visual fields and often culminates in legal or complete blindness. In addition to pigment deposition, progression of the disease is accompanied by retinal atrophy

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“…As was true for the crx-/crx-mice, the IMPDH1 transcript was significantly reduced in the rho-/rho-knockout retinas. Sequencing in the original, Spanish RP10 family (Jordan et al, 1993) revealed a missense mutation, Arg224Pro, segregating with disease. Thus two different approaches to identifying photoreceptor transcripts led to identification of the same RP10 gene, confirming the power of expression analysis to prioritize potential candidate genes.…”

Section: The Rp10 Genementioning

confidence: 99%

Identification of the RP1 and RP10 (IMPDH1) Genes Causing Autosomal Dominant RP

Daiger

Sullivan

Bowne

et al. 2003

Advances in Experimental Medicine and Biology

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Localization of an autosomal dominant retinitis pigmentosa gene to chromosome 7q

Cited by 119 publications

References 29 publications

Phenotypic Characterization of a Large Family With RP10 Autosomal-Dominant Retinitis Pigmentosa: An Asp226Asn Mutation in the IMPDH1 Gene

Phenotypic Characterization of a Large Family With RP10 Autosomal-Dominant Retinitis Pigmentosa: An Asp226Asn Mutation in the IMPDH1 Gene

Mapping the RP10 locus for autosomal dominant retinitis pigmentosa on 7q: refined genetic positioning and localization within a well-defined YAC contig.

Identification of the RP1 and RP10 (IMPDH1) Genes Causing Autosomal Dominant RP

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