Dataset Information

PAX6 gene analysis in irido-fundal coloboma.

ABSTRACT: To screen the paired box gene 6 (PAX6) gene in irido-fundal coloboma.The entire coding region of PAX6 including intron-exon boundaries was amplified from cases (n=30) and controls (n=30). All sequences were analyzed against the ensemble sequence (ENSG00000007372) for PAX6.DNA sequence analysis of patients and controls revealed a total of three nucleotide changes (g.31815391Cytosine>Thymine; Glycine72Glycine and g.31812215Thymine>Guanine) of which one was neutral/synonymous change and the remaining two were intronic changes. Of these 3 changes, 2 were novel and one was already reported change. All these changes were non-pathogenic, according to in silico analysis.In our study no pathogenic PAX6 mutation were identified. This suggests involvement of other coloboma genes. This study expands the SNP spectrum of PAX6, only rare variations which are not causative have been found. Since this is a pilot study in the north Indian population, results should be confirmed in different populations by similar studies. Familial cases are required for determining the underlying genetic loci accounting for this clinical phenotype and may lead to better understanding of disease pathogenesis.

SUBMITTER: Kumar K

PROVIDER: S-EPMC3108901 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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PAX6 gene analysis in irido-fundal coloboma.

Kumar Kishlay K Tanwar Mukesh M Naithani Prashant P Insaan Rajpal R Garg Satpal S Venkatesh Pradeep P Dada Rima R

Molecular vision 20110527

<h4>Purpose</h4>To screen the paired box gene 6 (PAX6) gene in irido-fundal coloboma.<h4>Methods</h4>The entire coding region of PAX6 including intron-exon boundaries was amplified from cases (n=30) and controls (n=30). All sequences were analyzed against the ensemble sequence (ENSG00000007372) for PAX6.<h4>Results</h4>DNA sequence analysis of patients and controls revealed a total of three nucleotide changes (g.31815391Cytosine>Thymine; Glycine72Glycine and g.31812215Thymine>Guanine) of which o ...[more]

PMID: 21655361

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Project description:PurposeTo report on a clinical and genetic investigation of a large, multigenerational South African family of mixed ancestry with autosomal dominant congenital cataracts, coloboma, and nystagmus.MethodsOphthalmic examination was performed in 27 individuals from the same admixed South African family. DNA was sampled from either peripheral blood or buccal swabs in all 27 individuals, and whole genome sequencing was performed in six individuals. Sanger sequencing was used to validate the probable mutation in the remaining family members.ResultsTwenty-seven family members with 19 affected individuals were included in the study. The predominant phenotype, with highly variable expression, was congenital cataract (14 individuals), posterior segment coloboma (17 individuals), and nystagmus (18 individuals). Other features present included high myopia, microcornea, and strabismus. An R208W mutation in PAX6 (dbSNP rs757259413; HGMD CM930572; NM_000280.3:c.622G>A; NP_000271.1:p.Arg208Trp) was identified as being the most probable pathogenic mutation. Cosegregation of the mutation with the phenotype was confirmed in all 27 family members.ConclusionsPAX6 is a highly conserved gene crucial for normal oculogenesis, and although mutations within the gene may cause an array of ocular developmental abnormalities, most are associated with aniridia and aniridia-related ocular defects. The observation that PAX6 aniridia phenotypes are largely associated with nonsense mutations and milder non-aniridia phenotypes with missense mutations suggested that there may be specific genotype-phenotype correlations for the gene. The R208W mutation in PAX6 identified in this family challenges this theory as it has previously been reported in three unrelated families and is associated with aniridia and non-aniridia phenotypes across the four families. PAX6 with its wide phenotypic associations and highly variable expression should be considered a candidate gene in the diagnostic screen for any ocular developmental abnormality.

Dataset Information

PAX6 gene analysis in irido-fundal coloboma.

Publications

PAX6 gene analysis in irido-fundal coloboma.

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