| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Divisions of Molecular Genetics, 4Pathology, and 5Visual Science, Institute of Ophthalmology, University College London, United Kingdom; 3Moorfields Eye Hospital, London, United Kingdom; the 6Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham, United Kingdom; 7Birmingham Midlands Eye Hospital and Birmingham Children’s Hospital, Birmingham, United Kingdom; the 8Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom; and the 9Department of Ophthalmology, Addenbrookes Hospital, Cambridge, United Kingdom.
PURPOSE. To test the incidence of mutations in RPGR ORF15 in six families with X-linked progressive retinal degeneration (cone-rod dystrophy [XLCORD], macular or cone dystrophy) and to undertake a detailed phenotypic assessment of families in whom ORF15 mutations were identified.
METHODS. To amplify and sequence ORF15 in its entirety, a cloning strategy was developed. Families with mutations in ORF15 underwent electrophysiological testing, color vision assessment, color fundus photography, and fundus autofluorescence (AF) imaging.
RESULTS. Novel protein truncation mutations were identified in two families. In family A, a 2-bp mutation was identified in ORF15+A1094C G1095T, predicted to result in a truncated protein (E364D/E365X). In family B, a G-to-T transversion (ORF15+1176G>T) resulted in a nonsense mutation (G392X). Characteristics of phenotype in both families included progressive deterioration of central vision and subsequently night vision, mild photophobia, and moderate to high myopia. Ophthalmoscopic abnormalities were generally confined to the macula. A parafoveal ring of increased AF was observed, and electrophysiological evidence of a greater generalized abnormality in cone than rod responses were consistent with a cone–rod dystrophy phenotype.
CONCLUSIONS. The cloning strategy for ORF15 facilitated comprehensive sequence analysis in patients. Two families were identified with nonsense mutations, and clinical evaluation revealed them both to have a similar phenotype. The presence of a parafoveal ring of increased AF was an early indicator of affected status in these families. No disease-causing mutations in ORF15 were detected in four other families, suggesting that ORF15 mutations may not be the most common cause of XLCORD.
This article has been cited by other articles:
|
|
 |
|
  S. Brunner, S. Skosyrski, R. Kirschner-Schwabe, K.-P. Knobeloch, J. Neidhardt, S. Feil, E. Glaus, U. F. O. Luhmann, K. Ruther, and W. Berger Cone versus Rod Disease in a Mutant Rpgr Mouse Caused by Different Genetic Backgrounds Invest. Ophthalmol. Vis. Sci., February 1, 2010; 51(2): 1106 - 1115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J B Ruddle, N D Ebenezer, L S Kearns, L E Mulhall, D A Mackey, and A J Hardcastle RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population Br J Ophthalmol, September 1, 2009; 93(9): 1151 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brunner, D. Colman, A. J. Travis, U. F.O. Luhmann, W. Shi, S. Feil, C. Imsand, J. Nelson, C. Grimm, T. Rulicke, et al. Overexpression of RPGR Leads to Male Infertility in Mice Due to Defects in Flagellar Assembly Biol Reprod, October 1, 2008; 79(4): 608 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Poloschek, B. Kloeckener-Gruissem, L. L. Hansen, M. Bach, and W. Berger Syndromic Choroideremia: Sublocalization of Phenotypes Associated with Martin-Probst Deafness Mental Retardation Syndrome Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 4096 - 4104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Walia, G. A. Fishman, A. Swaroop, K. E. H. Branham, M. Lindeman, M. Othman, and R. G. Weleber Discordant Phenotypes in Fraternal Twins Having an Identical Mutation in Exon ORF15 of the RPGR Gene Arch Ophthalmol, March 1, 2008; 126(3): 379 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A G Robson, M Michaelides, V A Luong, G E Holder, A C Bird, A R Webster, A T Moore, and F W Fitzke Functional correlates of fundus autofluorescence abnormalities in patients with RPGR or RIMS1 mutations causing cone or cone rod dystrophy Br J Ophthalmol, January 1, 2008; 92(1): 95 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-B. Jin, F. Gu, X. Ma, and N. Nao-i Identification of a Novel RPGR Exon ORF15 Mutation in a Family With X-linked Retinitis Pigmentosa Arch Ophthalmol, October 1, 2007; 125(10): 1407 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3283 - 3291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Tsang, V. Vaclavik, A. C. Bird, A. G. Robson, and G. E. Holder Novel Phenotypic and Genotypic Findings in X-Linked Retinoschisis Arch Ophthalmol, February 1, 2007; 125(2): 259 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q Zhang, X Guo, X Xiao, X Jia, S Li, and J F Hejtmancik Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1. J. Med. Genet., May 1, 2006; 43(5): e20 - e20. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
