[HTML][HTML] A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia
N Weisschuh, B Wissinger, E Gramer - Molecular vision, 2012 - ncbi.nlm.nih.gov
N Weisschuh, B Wissinger, E Gramer
Molecular vision, 2012•ncbi.nlm.nih.govPurpose 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 …
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 …
Abstract
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 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.
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