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Publication year
2010Source
Investigative Ophthalmology and Visual Science, 51, 3, (2010), pp. 1628-1635ISSN
Annotation
1 maart 2010
Publication type
Article / Letter to editor

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Organization
Human Genetics
Journal title
Investigative Ophthalmology and Visual Science
Volume
vol. 51
Issue
iss. 3
Page start
p. 1628
Page end
p. 1635
Subject
NCMLS 6: Genetics and epigenetic pathways of diseaseAbstract
PURPOSE: The majority of patients with X chromosome-linked retinitis pigmentosa (XlRP) carry mutations in the RPGR gene. The authors studied whether patients with RPGR mutations show additional splice defects that may interfere with RPGR properties. METHODS: Patient-derived cell lines with RPGR mutations were raised in suspension. To verify mutations, direct sequencing of PCR products was performed. Patient-specific alterations in RPGR splicing were analyzed by RT-PCR and confirmed by sequencing. Tissue-specific expression levels of RPGR splice variants were quantified by real-time PCR using pools of different human donor tissues. RESULTS: The authors analyzed the splicing of RPGR in seven RP patient-derived lymphoblastoid cell lines carrying hemizygous RPGR mutations. In three patient cell lines, they identified and characterized splice defects that were present in addition to a mutation. These splice defects were likely to interfere with normal RPGR properties. Furthermore, they identified four novel RPGR transcripts, either containing a new exon termed 11a or skipping the constitutive exons 12, 14, and 15. Novel and known RPGR isoforms were found to be differentially regulated in several human tissues. In human retina, approximately 10% of RPGR transcripts are alternatively spliced between exons 9 and 15. CONCLUSIONS: These findings show that splicing of RPGR is precisely regulated in a tissue-dependent fashion and suggest that mutations in RPGR frequently interfere with the expression of alternative transcript isoforms. These results implicate the importance of RPGR transcript analysis in patients with RP. The authors further discuss RPGR splicing as a modifier of different disease phenotypes described in patients with XlRP.
This item appears in the following Collection(s)
- Academic publications [202863]
- Electronic publications [101087]
- Faculty of Medical Sciences [80039]
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