title: A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia.
abstract: OBJECTIVE
  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.
authors.affiliation: Centre for Ophthalmology, Institute for Ophthalmic Research, Molecular Genetics Laboratory, Tuebingen, Germany. nicole.weisschuh@uni-tuebingen.de
authors.forename: Nicole
authors.initials: N
authors.lastname: Weisschuh
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Eugen
authors.initials: E
authors.lastname: Gramer
mesh_terms: D015783:Aniridia / Q000235:genetics*; D001483:Base Sequence; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005858:Germany; D057809:HEK293 Cells; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection; D044465:White People / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D022821:RNA Splice Sites; D012097:Repressor Proteins