Dataset Information

PAX6 analysis of one family and one sporadic patient from southern China with classic aniridia.

ABSTRACT: To investigate the paired box gene 6 (PAX6) in three patients from southern China presenting with classic aniridia: two patients from two successive generations of one family and one sporadic patient.All the available members from two successive generations of one family and one sporadic patient underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from leukocytes of peripheral blood collected from the two generations of family members, the sporadic patient and 100 unrelated control subjects from the same population. Exons 1-13 of the PAX6 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. The ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, and Pentacam and Goldmann perimetry.The three patients were affected with aniridia accompanied by microcornea, microphthalmia, and nystagmus. A heterozygous PAX6 frameshift mutation, c.891del A(p.Gln297HisfsX68) in exon 10, was identified in the affected individuals and not in any of the unaffected family members, including the unaffected family members of the proband patient's generation. One novel mutation, c.607C>T(Arg203X) in exon 8, was detected in the unrelated sporadic patient.Although PAX6 gene mutations and polymorphisms have been reported from various ethnic groups, we report for the first time the identification of two new PAX6 gene mutations in Chinese aniridia patients.

SUBMITTER: Lin Y

PROVIDER: S-EPMC3235534 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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PAX6 analysis of one family and one sporadic patient from southern China with classic aniridia.

Lin Ying Y Liu Xialin X Liang Xuanwei X Li Baoxin B Jiang Shuhong S Ye Shaobi S Yang Huiqin H Lou Bingsheng B Liu Yizhi Y

Molecular vision 20111126

<h4>Purpose</h4>To investigate the paired box gene 6 (PAX6) in three patients from southern China presenting with classic aniridia: two patients from two successive generations of one family and one sporadic patient.<h4>Methods</h4>All the available members from two successive generations of one family and one sporadic patient underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from leukocytes of peripheral blood collected from the two generations of family members ...[more]

PMID: 22171157

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Project description:To report the clinical and genetic study of patients with autosomal dominant aniridia.We studied ten patients with aniridia from three families of Egyptian origin. All patients underwent full ophthalmologic, general and neurological examination, and blood drawing. Cerebral magnetic resonance imaging was performed in the index case of each family. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of the Paired Box gene 6 (PAX6) was performed after PCR amplification. Phenotype description, including ophthalmic and cerebral anomalies, mutation detection in PAX6 and phenotype-genotype correlation was acquired.Common features observed in the three families included absence of iris tissue, corneal pannus with different degrees of severity, and foveal hypoplasia with severely reduced visual acuity. In Families 2 and 3, additional findings, such as lens dislocation, lens opacities or polar cataract, and glaucoma, were observed. We identified two novel (c.170-174delTGGGC [p.L57fs17] and c.475delC [p.R159fs47]) and one known (c.718C>T [p.R240X]) PAX6 mutations in the affected members of the three families. Systemic and neurological examination was normal in all ten affected patients. Cerebral magnetic resonance imaging showed absence of the pineal gland in all three index patients. Severe hypoplasia of the brain anterior commissure was associated with the p.L57fs17 mutation, absence of the posterior commissure with p.R159fs47, and optic chiasma atrophy and almost complete agenesis of the corpus callosum with p.R240X.We identified two novel PAX6 mutations in families with severe aniridia. In addition to common phenotype of aniridia and despite normal neurological examination, absence of the pineal gland and interhemispheric brain anomalies were observed in all three index patients. The heterogeneity of PAX6 mutations and brain anomalies are highlighted. This report emphasizes the association between aniridia and brain anomalies with or without functional impact, such as neurodevelopment delay or auditory dysfunction.

Project description:PURPOSE: To determine the genetic and genomic alterations underlying classic aniridia in Saudi Arabia, a region with social preference for consanguineous marriage. METHODS: Prospective study of consecutive patients referred to a pediatric ophthalmologist in Saudi Arabia (2005-2009). All patients had paired box gene 6 (PAX6) analysis (sequencing and multiplex ligation-dependent probe amplification analysis if sequencing was normal). If PAX6 analysis was negative, the following were performed: candidate gene sequencing (forkhead box C1 [FOXC1], paired-like homeodomain transcription factor 2 [PITX2], cytochrome P450, family 1, subfamily B [CYP1B1], paired-like homeodomain transcription factor 3 [PITX3], and v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog [MAF]) and molecular karyotyping by array competitive genomic hybridization (250K single nucleotide polymorphism (SNP) arrays). RESULTS: All 12 probands (4 months-25 years of age; four boys and eight girls) had lens opacity and foveal hypoplasia in addition to no grossly visible iris. Four cases were familial. All cases were products of consanguineous unions except for three, one of which was endogamous. Heterozygous PAX6 mutations (including two novel mutations) were detectable in all but two cases, both of which were sporadic. In one of these two cases, the phenotype segregated with homozygosity for a previously-reported pathogenic missense FOXC1 variant (p.P297S) when homozygosity for chromosome 11q24.2 deletion (chr11:125,001,547-125,215,177 [rs114259885; rs112291840]) was also present. In the other, no genetic or genomic abnormalities were found. CONCLUSIONS: The classic aniridia phenotype in Saudi Arabia is typically caused by heterozygous PAX6 mutations, even in the setting of enhanced homozygosity from recent shared parental ancestry. For PAX6-negative cases, interaction between missense variation in an anterior segment developmental gene and copy number variation elsewhere in the genome may be a potential mechanism for the phenotype.

Dataset Information

PAX6 analysis of one family and one sporadic patient from southern China with classic aniridia.

Publications

PAX6 analysis of one family and one sporadic patient from southern China with classic aniridia.

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