Dataset Information

A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia.

ABSTRACT: To identify the underlying genetic cause in a two generation German family diagnosed with isolated aniridia.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.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.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.

SUBMITTER: Weisschuh N

PROVIDER: S-EPMC3324353 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia.

Weisschuh Nicole N Wissinger Bernd B Gramer Eugen E

Molecular vision 20120329

<h4>Purpose</h4>To identify the underlying genetic cause in a two generation German family diagnosed with isolated aniridia.<h4>Methods</h4>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.<h4>Results</h4>We identified a PAX6 sequence variant at the splice donor site (+5) of intro ...[more]

PMID: 22509105

Similar Datasets

Project description:Aniridia and congenital cataract represent rare but severe developmental ocular conditions. We examined 33 probands from France for mutations in several transcription factors associated with these phenotypes, the forkhead box E3 (FOXE3), paired box gene 6 (PAX6), paired-like homeodomain transcription factor 2 (PITX2), and paired-like homeodomain transcription factor 3 (PITX3) genes.Out of 33 probands, 27 were affected with congenital cataract while the remaining six were affected with aniridia (with or without cataract). The coding regions of FOXE3, PAX6, PITX2, and PITX3 were examined by direct DNA sequencing of gene-specific PCR products.A novel dominant mutation at the stop codon of FOXE3, c.959G>C (p.X320SerextX72), was identified in a patient with congenital cataract. Another novel FOXE3 sequence change, c.571-579dup (p.Tyr191_Pro193dup), was identified in a patient with aniridia, mild lens opacities, and some additional ocular defects; this patient was also found to carry a nonsense mutation in PAX6. PAX6 mutations were identified in two additional probands with aniridia and cataracts. None of the observed sequence alterations were found in normal controls. No mutations were identified in PITX2 or PITX3.The p.X320SerextX72 mutation is only the fourth FOXE3 allele associated with a dominant phenotype since the majority of FOXE3 mutations appear to be recessive with no phenotype observed in heterozygous carriers. The encoded protein is predicted to contain a complete normal sequence followed by seventy-two erroneous amino acids; the position and effect of this mutation are similar to two of the previously reported dominant changes, suggesting a common mechanism for dominant alleles. The p.Tyr191_Pro193dup is predicted to result in an in-frame duplication of three amino acids; however, the contribution of this mutation to the phenotype is unclear since the affected patient also carries a nonsense mutation in PAX6 which acts upstream of FOXE3 in the molecular pathway. The identified PAX6 mutations correspond to the two most commonly observed mutant alleles and demonstrate phenotypes that are consistent with the previously reported spectrum.

Dataset Information

A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia.

Publications

A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets