| Evaluation of human diacylglycerol kinase(iota), DGKI, a homolog of Drosophila rdgA, in inherited retinopathy mapping to 7q. | |
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MedLine Citation:
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PMID: 10706894 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To determine the genomic organization of diacylglycerol kinase(iota) and to test whether defects in this gene are present in individuals affected with autosomal dominant retinitis pigmentosa (adRP). Diacylglycerol kinase(iota) has been mapped to the RP10 locus on 7q and shows 49% sequence similarity to the Drosophila DGK2 rdgA gene. Since mutations in the DGK2 rdgA gene cause photoreceptor degeneration in Drosophila, it is possible that mutations in diacylglycerol kinase(iota) could be responsible for human retinal degeneration. METHODS: DNA sequence from genomic clones containing diacylglycerol kinase(iota) was compared with the cDNA sequence to identify intron/exon boundaries. Single-strand conformational analysis and PCR product sequencing were used to screen members of one family previously mapped to the RP10 locus and 47 small unmapped families with autosomal dominant retinitis pigmentosa. RESULTS: Diacylglycerol kinase(iota) is divided into 35 exons with the initiation codon being present in exon 2. Mutational analysis found a missense change (Lys153Phe) in three adRP families; however, it did not segregate with disease in one of the families. Silent substitutions were seen in codons 865 and 875. Intronic variation was detected in the amplifications of exons 3,5,18, 28, and 32; these do not affect splice site consensus sequences. Typing of a polymorphic variant detected in intron 31 in members of the RP10 family gave a LOD score of -4.2 at 0% recombination. CONCLUSIONS: No evidence of disease-associated mutations was found in any of the samples tested. Based on the linkage data and mutation screening, diacylglycerol kinase(iota) is excluded as a candidate for the RP10 form of adRP and cannot be a frequent cause of other forms of adRP. Mutations in diacylglycerol kinase(iota) may yet be the cause of recessive forms of retinal degeneration in humans, either in homozygous or compound heterozygous forms. The data provided here will permit testing of this hypothesis. |
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Authors:
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S J Bowne; L S Sullivan; L Ding; E Traer; S M Prescott; D G Birch; A Kennan; P Humphries; S P Daiger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2000-02-22 |
Journal Detail:
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Title: Molecular vision Volume: 6 ISSN: 1090-0535 ISO Abbreviation: Mol. Vis. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-03-16 Completed Date: 2000-03-16 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 9605351 Medline TA: Mol Vis Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 6-9 Citation Subset: IM |
Affiliation:
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Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science, The University of Texas-Houston Health Science Center, Houston, TX, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AF219907; AF219939 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Chromosome Mapping Chromosomes, Human, Pair 7* DNA Mutational Analysis Diacylglycerol Kinase / genetics* Drosophila / enzymology, genetics Exons Female Humans Introns Male Molecular Sequence Data Polymorphism, Genetic Retinitis Pigmentosa / enzymology, genetics* |
| Grant Support | |
ID/Acronym/Agency:
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EY07142/EY/NEI NIH HHS; R01 EY007142-12A2/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.1.107/Diacylglycerol Kinase |
| Comments/Corrections | |
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