| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Jules Stein Eye Institute and the 6 Molecular Biology Institute, University of California Los Angeles School of Medicine; the 2 Biology Department, Loyola Marymount University, Los Angeles, California; the 3 Molecular Medicine Unit, University of Leeds, United Kingdom; 4 Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago; and the 5 Scheie Eye Institute, University of Pennsylvania, Philadelphia.
PURPOSE. To determine the locus of the mutant gene causing autosomal recessive cone–rod dystrophy (arCRD) in a consanguineous pedigree, to evaluate a candidate gene expressed in retina that maps to this locus, and to estimate the percentage of arCRD cases caused by mutations in this gene.
METHODS. DNAs from family members were genotyped for markers covering the entire genome at an average spacing of approximately 9 centimorgans (cM). The data were input into a pedigree computer program to produce output files used to calculate lod scores. Significant linkage was revealed at 8cen, prompting the genotyping of a number of additional markers. Exons of a candidate gene were sequenced directly by standard fluorescent dideoxy methods. Haplotype analysis was performed with markers in this locus in 13 multiplex and 2 simplex CRD families in which neither parent had disease.
RESULTS. Four-point linkage analysis gave a maximum lod score of approximately 7.6 at both D8S1769 and GATA101H09 in the large consanguineous family. Recombination events defined an interval of 8.7 cM between D8S1820 and D8S532 within which the gene must lie. This 8p11 locus (CORD9) is immediately distal to but distinct from the RP1 autosomal dominant RP (adRP) locus. Two islands of homozygosity were found in this locus: The alleles of 6 of 10 markers in one of the islands and 2 of 4 in the other were homozygous. The UniGene cluster Hs.8719 (UniGene System, provided by the National Center for Biotechnology Information and available at http://www.ncbi.nlm.nih.gov/UniGene), which tags a gene with significant homology to Dual Specificity Phosphatase 3, maps within the CORD9 interval and is highly expressed in the retina. To evaluate this gene as a potential disease candidate, intron–exon structure was determined, and exons were screened in the consanguineous family. No variants were found that could be related to disease. Haplotype analysis of 15 other families with CRD, using markers at CORD9, excluded this locus in 9 of 15.
CONCLUSIONS. A new arCRD locus (CORD9) has been identified corresponding to a yet unidentified gene in the 8.7-cM interval D8S1820-D8S532. No mutations were found in one candidate gene in affected members of the primary study family. Haplotype analysis of a cohort of 13 multiplex and 2 simplex families with CRD ruled out the CORD9 gene in 9 of 15 of the families. To date, a total of 126 loci carrying gene mutations causing various forms of retinal degeneration have been mapped, and the mutant gene has been identified in 64 of them. However, only 2 loci for arCRD have been documented. This is the report of a third.
This article has been cited by other articles:
|
|
 |
|
  A. C. Wiik, C. Wade, T. Biagi, E.-O. Ropstad, E. Bjerkas, K. Lindblad-Toh, and F. Lingaas A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund Genome Res., September 1, 2008; 18(9): 1415 - 1421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Michaelides, G E Holder, D M Hunt, F W Fitzke, A C Bird, and A T Moore A detailed study of the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with mutation in the gene for RIM1 Br. J. Ophthalmol., February 1, 2005; 89(2): 198 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Hameed, A Abid, A Aziz, M Ismail, S Q Mehdi, and S Khaliq Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy J. Med. Genet., August 1, 2003; 40(8): 616 - 619. [Full Text]
|
|
|
|
 |
|
 G. A. Fishman, E. M. Stone, D. A. Eliason, C. M. Taylor, M. Lindeman, and D. J. Derlacki ABCA4 Gene Sequence Variations in Patients With Autosomal Recessive Cone-Rod Dystrophy Arch Ophthalmol, June 1, 2003; 121(6): 851 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Klevering, A. Blankenagel, A. Maugeri, F. P. M. Cremers, C. B. Hoyng, and K. Rohrschneider Phenotypic Spectrum of Autosomal Recessive Cone-Rod Dystrophies Caused by Mutations in the ABCA4 (ABCR) Gene Invest. Ophthalmol. Vis. Sci., June 1, 2002; 43(6): 1980 - 1985. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
