Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: Paucity of mutations in the coding region, but splice defects in two families
(1997) In American Journal of Human Genetics 61(3). p.571-580- Abstract
- X-linked retinitis pigmentosa (XLRP) is a severe form of inherited progressive retinal degeneration. The RP3 (retinitis pigmentosa type 3) locus at Xp21.1 is believed to account for the disease in the majority of XLRP families. Linkage analysis and identification of patients with chromosomal deletion have refined the location of the RP3 locus and recently have led to the cloning of the RPGR (retinitis pigmentosa GTPase regulator) gene, which has been shown to be mutated in 10%15% of XLRP patients. In order to systematically characterize the RPGR mutations, we identified 11 retinitis pig-mentosa type III (RP3) families by haplotype analysis. Sequence analysis of the PCR-amplified genomic DNA from patients representing these RP3 families did... (More)
- X-linked retinitis pigmentosa (XLRP) is a severe form of inherited progressive retinal degeneration. The RP3 (retinitis pigmentosa type 3) locus at Xp21.1 is believed to account for the disease in the majority of XLRP families. Linkage analysis and identification of patients with chromosomal deletion have refined the location of the RP3 locus and recently have led to the cloning of the RPGR (retinitis pigmentosa GTPase regulator) gene, which has been shown to be mutated in 10%15% of XLRP patients. In order to systematically characterize the RPGR mutations, we identified 11 retinitis pig-mentosa type III (RP3) families by haplotype analysis. Sequence analysis of the PCR-amplified genomic DNA from patients representing these RP3 families did not reveal any causative mutation in RPGR exons 219, spanning > 98% of the coding region. In patients from two families, we identified transition mutations in the intron region near splice sites (IVS10/3 and IVS13-8). RNA analysis showed that both splice-site mutations resulted in the generation of aberrant RPGR transcripts. Our results support the hypothesis that mutations in the reported RPGR gene are not a common defect in the RP3 subtype of XLRP and that a majority of causative mutations may reside either in as yet unidentified RPGR exons or in another nearby gene at Xp21.1. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1112460
- author
- Fujita, Ricardo ; Buraczynska, Monika ; Gieser, Linn ; Wu, Weiping ; Forsythe, Patricia ; Abrahamson, Magnus LU ; Jacobsson, Samuel G ; Sieving, Paul A ; Andréasson, Sten LU and Swaroop, Anand
- organization
- publishing date
- 1997
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Human Genetics
- volume
- 61
- issue
- 3
- pages
- 571 - 580
- publisher
- Cell Press
- external identifiers
-
- scopus:16944362660
- ISSN
- 0002-9297
- DOI
- 10.1086/515523
- language
- English
- LU publication?
- yes
- id
- 856fb104-e31b-4610-8a94-62b466fe981c (old id 1112460)
- date added to LUP
- 2016-04-01 12:09:08
- date last changed
- 2022-03-05 19:38:35
@article{856fb104-e31b-4610-8a94-62b466fe981c, abstract = {{X-linked retinitis pigmentosa (XLRP) is a severe form of inherited progressive retinal degeneration. The RP3 (retinitis pigmentosa type 3) locus at Xp21.1 is believed to account for the disease in the majority of XLRP families. Linkage analysis and identification of patients with chromosomal deletion have refined the location of the RP3 locus and recently have led to the cloning of the RPGR (retinitis pigmentosa GTPase regulator) gene, which has been shown to be mutated in 10%15% of XLRP patients. In order to systematically characterize the RPGR mutations, we identified 11 retinitis pig-mentosa type III (RP3) families by haplotype analysis. Sequence analysis of the PCR-amplified genomic DNA from patients representing these RP3 families did not reveal any causative mutation in RPGR exons 219, spanning > 98% of the coding region. In patients from two families, we identified transition mutations in the intron region near splice sites (IVS10/3 and IVS13-8). RNA analysis showed that both splice-site mutations resulted in the generation of aberrant RPGR transcripts. Our results support the hypothesis that mutations in the reported RPGR gene are not a common defect in the RP3 subtype of XLRP and that a majority of causative mutations may reside either in as yet unidentified RPGR exons or in another nearby gene at Xp21.1.}}, author = {{Fujita, Ricardo and Buraczynska, Monika and Gieser, Linn and Wu, Weiping and Forsythe, Patricia and Abrahamson, Magnus and Jacobsson, Samuel G and Sieving, Paul A and Andréasson, Sten and Swaroop, Anand}}, issn = {{0002-9297}}, language = {{eng}}, number = {{3}}, pages = {{571--580}}, publisher = {{Cell Press}}, series = {{American Journal of Human Genetics}}, title = {{Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: Paucity of mutations in the coding region, but splice defects in two families}}, url = {{http://dx.doi.org/10.1086/515523}}, doi = {{10.1086/515523}}, volume = {{61}}, year = {{1997}}, }