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Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population.

ABSTRACT: This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC).We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination.By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes.From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC.

SUBMITTER: Li D

PROVIDER: S-EPMC4896834 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population.

Li Dan D Wang Siying S Ye Hongfei H Tang Yating Y Qiu Xiaodi X Fan Qi Q Rong Xianfang X Liu Xin X Chen Yuhong Y Yang Jin J Lu Yi Y

Molecular vision 20160608

<h4>Purpose</h4>This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC).<h4>Methods</h4>We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subje ...[more]

PMID: 27307692

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Project description:BACKGROUND: B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China. METHODS: We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes. RESULTS: Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status. CONCLUSION: These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.

Project description:Purpose:To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function. Results:The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation. Conclusions:We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract.WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.

Dataset Information

Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population.

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Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population.

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