| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Division of Molecular Genetics, Institute of Ophthalmology, University College London, London, United Kingdom; the 3Moorfields Eye Hospital, London, United Kingdom; and the 4Academic Department of Surgery, St. Bartholomews and the Queen Mary’s School of Medicine and Dentistry, University of London, London, United Kingdom.
PURPOSE. To investigate whether the incomplete penetrance phenotype characteristic of adRP families linked to chromosome 19q13.4 (RP11) with mutations in the PRPF31 gene is due to differentially expressed wild-type alleles in symptomatic and asymptomatic individuals.
METHODS. Real-time quantitative RT-PCR was performed on RNA from lymphoblastoid cell lines derived from a large adRP family (RP856/AD5) that segregates an 11bp deletion in exon 11 of PRPF31. The mRNA levels from only the wild-type allele of PRPF31 were assayed using a probe designed across the deletion. The Mann-Whitney U test was used to compare the median mRNA copy numbers of the symptomatic with the asymptomatic carriers of the mutant PRPF31 allele. The PRPF31 protein levels from symptomatic and asymptomatic individuals were also assayed by Western blot analysis using an antibody specific to the wild-type PRPF31 protein.
RESULTS. The use of cell lines was validated by the observation that cell transformation did not alter PRPF31 expression in the cell lines compared with nucleated blood cells and donor retinas. A significant difference in wild-type PRPF31 mRNA levels was observed between symptomatic and asymptomatic individuals (P < 0.001) and was supported by Western blot analysis of the PRPF31 protein.
CONCLUSIONS. Partial penetrance in RP11 could be due to the coinheritance of a PRPF31 gene defect and a low-expressed wild-type allele. This study revealed a potential avenue for future therapy in that it appears the moderate overexpression of wild-type PRPF31 may prevent clinical manifestation of the disease.
This article has been cited by other articles:
|
|
 |
|
  C. Zeitz, A. K. Gross, D. Leifert, B. Kloeckener-Gruissem, S. D. McAlear, J. Lemke, J. Neidhardt, and W. Berger Identification and Functional Characterization of a Novel Rhodopsin Mutation Associated with Autosomal Dominant CSNB Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 4105 - 4114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Ghazawy, K Springell, V Gauba, M A McKibbin, and C F Inglehearn Dominant retinitis pigmentosa phenotype associated with a new mutation in the splicing factor PRPF31 Br. J. Ophthalmol., October 1, 2007; 91(10): 1411 - 1413. [Full Text] [PDF]
|
|
|
|
|
|
A. Arora, G. J. McKay, and D. A. C. Simpson Prediction and Verification of miRNA Expression in Human and Rat Retinas Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 3962 - 3967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Waseem, V. Vaclavik, A. Webster, S. A. Jenkins, A. C. Bird, and S. S. Bhattacharya Mutations in the Gene Coding for the Pre-mRNA Splicing Factor, PRPF31, in Patients with Autosomal Dominant Retinitis Pigmentosa Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1330 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Sullivan, S. J. Bowne, C. R. Seaman, S. H. Blanton, R. A. Lewis, J. R. Heckenlively, D. G. Birch, D. Hughbanks-Wheaton, and S. P. Daiger Genomic Rearrangements of the PRPF31 Gene Account for 2.5% of Autosomal Dominant Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4579 - 4588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Sullivan, S. J. Bowne, D. G. Birch, D. Hughbanks-Wheaton, J. R. Heckenlively, R. A. Lewis, C. A. Garcia, R. S. Ruiz, S. H. Blanton, H. Northrup, et al. Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3052 - 3064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Ziviello, F Simonelli, F Testa, M Anastasi, S B Marzoli, B Falsini, D Ghiglione, C Macaluso, M P Manitto, C Garre, et al. Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families J. Med. Genet., July 1, 2005; 42(7): e47 - e47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Y Gregory-Evans, M J Williams, S Halford, and K Gregory-Evans Ocular coloboma: a reassessment in the age of molecular neuroscience J. Med. Genet., December 1, 2004; 41(12): 881 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. van Heyningen and P. L. Yeyati Mechanisms of non-Mendelian inheritance in genetic disease Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R225 - R233. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
