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| Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa |
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| Author(s): Maw MA, Kennedy B, Knight A, Bridges R, Roth KE, Mani EJ, Mukkadan JK, Nancarrow D, Crabb JW, Denton MJ |
| Source: NATURE GENETICS Volume: 17 Issue: 2 Pages: 198-200 Published: OCT 1997 |
| Times Cited: 165 References: 30 |
| Abstract: Inadequate levels of all-trans-retinol in the blood cause retinal dysfunction; hence, genes implicated in retinal vitamin-A metabolism represent candidates for inherited retinal degenerations(1,2). In the current study, molecular genetic analysis of a consanguineous pedigree segregating for non-syndromic autosomal recessive retinitis pigmentosa (arRP) indicated that the affected siblings were homozygous by descent for a G4763A nucleotide substitution in RLBP1, the gene encoding cellular retinaldehyde-binding protein (CRALBP). This substitution is predicted to replace an arginine with glutamine at residue 150. CRALBP is not expressed in photoreceptors but is abundant in the retinal pigment epithelium (RPE) and Muller cells of the neuroretina, where it carries 11-cis-retinol and 11-cis-retinaldehyde(3-5). When expressed in bacteria, recombinant CRALBP (rCRALBP) containing the R150Q substitution was less soluble than wild-type rCRALBP. Mutant rCRALBP was purified from the soluble cell lysate and the protein structure was verified by mass spectrometry. The mutant protein lacked the ability of bind 11-cis-retinaldehyde. These findings suggest that arRP in the current pedigree results from a lack of functional CRALBP, presumably leading to disruption of retinal vitamin-A metabolism. |
| Document Type: Article |
| Language: English |
| Reprint Address: Maw, MA (reprint author), UNIV OTAGO, DEPT BIOCHEM, POB 56, DUNEDIN, NEW ZEALAND |
Addresses:
1. W ALTON JONES CELL SCI CTR, PROT CHEM FACIL, LAKE PLACID, NY 12946 USA
2. LITTLE FLOWER MED RES CTR, ANGAMALLY 683572, KERALA INDIA
3. WOLSTON PK HOSP, QUEENSLAND CTR SCHIZOPHRENIA RES, BRISBANE, QLD AUSTRALIA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: XZ555 |
| ISSN: 1061-4036 |
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