Journal article
Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia
Molecular vision, Vol.16(183-84), pp.1705-1711
2010
PMCID: PMC2927439
PMID: 20806047
Abstract
Purpose: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Details
- Title: Subtitle
- Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia
- Creators
- Dominique Brémond-Gignac - Department of Pediatric Ophthalmology, St Victor University Hospital of Amiens, INSERM UMRS968, Vision Institute, Paris VI University, Picardie Jules Verne University, Amiens, FrancePierre Bitoun - Department of Genetics, Jean Verdier Paris-Nord University Hospital, APHP, Bondy, FranceLinda M Reis - Department of Pediatrics and Children’s Research Institute at the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, WIHenri Copin - Department of Cytogenetics and Reproduction Biology, CGO University Hospital of Amiens, Picardie Jules Verne University, Amiens, FranceJeffrey C Murray - Department of Pediatrics, The University of Iowa, Iowa City, IAElena V Semina - Department of Pediatrics and Children’s Research Institute at the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, WI
- Resource Type
- Journal article
- Publication Details
- Molecular vision, Vol.16(183-84), pp.1705-1711
- PMID
- 20806047
- PMCID
- PMC2927439
- NLM abbreviation
- Mol Vis
- ISSN
- 1090-0535
- eISSN
- 1090-0535
- Publisher
- Molecular Vision
- Language
- English
- Date published
- 2010
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025319402771
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