A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia
Please always quote using this URN: urn:nbn:de:bvb:20-opus-124379
- Purpose: To identify the underlying genetic cause in a two generation German family diagnosed with isolated aniridia. Methods: All patients underwent full ophthalmic examination. Mutation screening of the paired box gene 6 (PAX6) was performed by bidirectional Sanger sequencing. A minigene assay was applied to analyze transcript processing of mutant and wildtype PAX6 variants in HEK293 cells. Results: We identified a PAX6 sequence variant at the splice donor site (+5) of intron 12. This variant has been described before in another family withPurpose: To identify the underlying genetic cause in a two generation German family diagnosed with isolated aniridia. Methods: All patients underwent full ophthalmic examination. Mutation screening of the paired box gene 6 (PAX6) was performed by bidirectional Sanger sequencing. A minigene assay was applied to analyze transcript processing of mutant and wildtype PAX6 variants in HEK293 cells. Results: We identified a PAX6 sequence variant at the splice donor site (+5) of intron 12. This variant has been described before in another family with aniridia but has not been characterized at the transcript level. We could demonstrate that the mutant allele causes the skipping of exon 12 during transcript processing. The mutation is predicted to result in a ‘run on’ translation past the normal translational stop codon. Conclusions: A splice site mutation resulting in exon skipping was found in a family with autosomal dominant aniridia. The mutation is predicted to result in an enlarged protein with an extra COOH-terminal domain. This very likely affects the transactivation properties of the PAX6 protein.…
Author: | Nicole Weisschuh, Bernd Wissinger, Eugen Gramer |
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URN: | urn:nbn:de:bvb:20-opus-124379 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Augenklinik und Poliklinik |
Language: | English |
Parent Title (English): | Molecular Vision |
Year of Completion: | 2012 |
Volume: | 18 |
Pagenumber: | 751-757 |
Source: | Molecular Vision 2012; 18:174-180 http://www.molvis.org/molvis/v18/a20 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 617 Chirurgie und verwandte medizinische Fachrichtungen |
Release Date: | 2016/01/19 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung |