Article

Molecular analysis of the PAX6 gene for congenital aniridia in the Korean population: Identification of four novel mutations

Seoul St. Mary's Hospital, Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Molecular vision (Impact Factor: 2.25). 02/2012; 18:488-94.
Source: PubMed

ABSTRACT To analyze the paired box gene 6 (PAX6) in Korean patients with congenital aniridia.
Genomic DNA was isolated from peripheral blood leukocytes of 22 aniridia patients in 18 unrelated families. Polymerase chain reaction was performed for all 14 exons of PAX6 followed by bidirectional sequencing.
Fourteen different kinds of mutations were detected in 16 of 18 unrelated families (mutation detection rate: 88.9%), including four novel mutations; c.658G>T (p.Glu220*), c.464delG (p.Ser155Thrfs*52), c.87_90dupTGTA (p.Glu31Cysfs*26), and c.642A>C (p.Arg214Ser), among which the former three mutations induce premature termination of PAX6 protein translation. Approximately 92.9% of identified mutations lead to the premature termination of the protein resulting from 7 nonsense mutations (50.0%), 3 splicing errors (21.4%), 2 deletions (14.3%), and 1 insertion (7.1%).
Most of the mutations identified in Korean aniridia patients lead to the premature truncation of the PAX6 protein, supporting that PAX6 protein haploinsufficiency causes the classic aniridia phenotype. We also found four novel PAX6 mutations associated with aniridia.

0 Bookmarks
 · 
115 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aniridia is a rare panocular disorder characterized by iris hypoplasia and other associated eye anomalies. Heterozygous null mutations in paired box gene 6 (PAX6) are the major cause of the classic aniridia phenotype. This study aims to detect the mutational spectrum of PAX6 and associated phenotypes in southern Indian patients with sporadic and familial aniridia. Genomic DNA was isolated from peripheral blood from all participants. The coding regions and flanking intronic sequences of PAX6 were screened with Sanger sequencing in 30 probands with aniridia. The identified variations were further evaluated in available family members and 150 healthy controls. The pathogenic potential of the mutations were assessed using bioinformatics tools. Thirteen different mutations were detected in eight sporadic and five familial cases. Eleven novel mutations, including five insertions (c.7_10dupAACA, c.567dupC, c.704dupC, c.868dupA and c.753_754insTA), two deletions (c.242delC and c.249delT), and four splicing variants (c.10+1G>A, c.141G>A, c.141+4A>G and c.764A>G) were identified in this study. Clinical findings of the patients revealed phenotypic heterogeneity with the same or different mutations. This study reported 11 novel mutations and thus expanded the spectrum of PAX6 mutations. Interestingly, all mutations reported in this study were truncations, which confirms the hypothesis that haploinsufficiency of PAX6 causes the aniridia phenotype. Our observations revealed inter- and intrafamilial phenotypic variability with PAX6 mutations. The common ocular findings associated with PAX6 mutations were iris hypoplasia, nystagmus, and foveal hypoplasia reported in almost all cases, with cataract, glaucoma, and keratopathy reported in approximately 50% of the patients.
    Molecular vision 21:88-97. · 2.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aniridia is a rare, congenital ocular disorder with the characteristics of incomplete formation of the iris caused by the mutations of the paired box gene-6 (PAX6). To investigate the clinical characterization and the underlying genetic defect in a Chinese family with autosomal dominant aniridia, we recruited the family members who underwent comprehensive ophthalmic examination. A novel heterozygous PAX6 deletion mutation c.796 del G (p.A266 fs) (GenBank ID: KP255960) in exon 10 was exclusively observed in all affected individuals but not in any of the unaffected family members or unrelated controls. The PAX6 mRNA level was about 50% lower in patients with aniridia than in unaffected family members, indicating that this mutation caused nonsense-mediated mRNA decay. In conclusion, we identified a novel deletion mutation in the PAX6 gene resulting in an abnormal PAX6 COOH-terminal extension in the Chinese family with aniridia. Our study further expands the mutation spectrum of PAX6. Copyright © 2015. Published by Elsevier B.V.
    Gene 03/2015; DOI:10.1016/j.gene.2015.03.001 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To report 3 cases with unusual ophthalmic phenotypes of congenital aniridia. Interventional case series. A 10-day-old infant with cloudy and large cornea in both eyes, 1 month-old male with bilateral corneal opacity, and 27-year-old male with low vision. Complete ophthalmic examination and genetic evaluation. Case 1 was a neonate with concurrent presentation of congenital aniridia and glaucoma. Case 2 was diagnosed as congenital aniridia combined with Peters anomaly in both eyes. Case 3 had 2 unusual features of aniridia, which were asymmetric iris involvement and absence of limbal deficiency. It is important to perform thorough ophthalmologic evaluations in patients with congenital aniridia because of the possibilities of coexistence of other ocular abnormalities.
    Canadian Journal of Ophthalmology 08/2013; 48(4):340-2. DOI:10.1016/j.jcjo.2013.02.009 · 1.30 Impact Factor

Preview (2 Sources)

Download
4 Downloads
Available from