Neidhardt, John and Glaus, Esther and Lorenz, Birgit and Netzer, Christian and Li, Yuen and Schambeck, Maria and Wittmer, Mariana and Feil, Silke and Kirschner-Schwabe, Renate and Rosenberg, Thomas and Cremers, Frans P. M. and Bergen, Arthur A. B. and Barthelmes, Daniel and Baraki, Husnia and Schmid, Fabian and Tanner, Gaby and Fleischhauer, Johannes and Orth, Ulrike and Becker, Christian and Wegscheider, Erika and Nuernberg, Gudrun and Nuernberg, Peter and Bolz, Hanno Joern and Gal, Andreas and Berger, Wolfgang (2008) Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing. MOLECULAR VISION, 14 (129). pp. 1081-1093. ISSN 1090-0535,
Full text not available from this repository. (Request a copy)Abstract
Purpose: The goal of this study was to identify mutations in X-chromosomal genes associated with retinitis pigmentosa (RP) in patients from Germany, The Netherlands, Denmark, and Switzerland. Methods: In addition to all coding exons of RP2, exons 1 through 15, 9a, ORF15, 15a and 15b of RPGR were screened for mutations. PCR products were amplified from genomic DNA extracted from blood samples and analyzed by direct sequencing. In one family with apparently dominant inheritance of RP, linkage analysis identified an interval on the X chromosome containing RPGR, and mutation screening revealed a pathogenic variant in this gene. Patients of this family were examined clinically and by X-inactivation studies. Results: This study included 141 RP families with possible X-chromosomal inheritance. In total, we identified 46 families with pathogenic sequence alterations in RPGR and RP2, of which 17 mutations have not been described previously. Two of the novel mutations represent the most 3'-terminal pathogenic sequence variants in RPGR and RP2 reported to date. In exon ORF15 of RPGR, we found eight novel and 14 known mutations. All lead to a disruption of open reading frame. Of the families with suggested X-chromosomal inheritance, 35% showed mutations in ORF15. In addition, we found five novel mutations in other exons of RPGR and four in RP2. Deletions in ORF15 of RPGR were identified in three families in which female carriers showed variable manifestation of the phenotype. Furthermore, an ORF15 mutation was found in an RP patient who additionally carries a 6.4 kbp deletion downstream of the coding region of exon ORF15. We did not identify mutations in 39 sporadic male cases from Switzerland. Conclusions: RPGR mutations were confirmed to be the most frequent cause of RP in families with an X-chromosomal inheritance pattern. We propose a screening strategy to provide molecular diagnostics in these families.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RPGR EXON ORF15; MULTIPOINT LINKAGE ANALYSIS; NUCLEOTIDE-EXCHANGE FACTOR; POSITIONAL CLONING; GENE; RP2; LOCUS; DEGENERATION; DYSTROPHY; MAPS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Ophthalmologie, Strabismologie und Ophthalmogenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Oct 2020 10:20 |
| Last Modified: | 29 Oct 2020 10:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30747 |
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