| Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa. | |
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MedLine Citation:
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PMID: 20673862 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP. |
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Authors:
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Dikla Bandah-Rozenfeld; Rob W J Collin; Eyal Banin; L Ingeborgh van den Born; Karlien L M Coene; Anna M Siemiatkowska; Lina Zelinger; Muhammad I Khan; Dirk J Lefeber; Inbar Erdinest; Francesco Testa; Francesca Simonelli; Krysta Voesenek; Ellen A W Blokland; Tim M Strom; Caroline C W Klaver; Raheel Qamar; Sandro Banfi; Frans P M Cremers; Dror Sharon; Anneke I den Hollander |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-30 |
Journal Detail:
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Title: American journal of human genetics Volume: 87 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-10 Completed Date: 2010-09-01 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 199-208 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Amino Acid Sequence Animals Base Sequence COS Cells Cercopithecus aethiops Chromosome Mapping Chromosome Segregation / genetics DNA Mutational Analysis Female Fundus Oculi Genes, Recessive / genetics* Genetic Linkage Homozygote Humans Male Middle Aged Molecular Sequence Data Mutant Proteins / chemistry, genetics, metabolism Mutation / genetics* Pedigree Proteoglycans / chemistry, genetics* Retinitis Pigmentosa / genetics* Subcellular Fractions / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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TGM06D01//Telethon |
| Chemical | |
Reg. No./Substance:
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0/IMPG2 protein, human; 0/Mutant Proteins; 0/Proteoglycans |
| Comments/Corrections | |
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