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Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract.

ABSTRACT: The study aims to explore the correlations of the single nucleotide polymorphisms (SNPs) of CRYAA and CRYAB with the risk and clinicopathological features of children with congenital cataract.The study enrolled 168 children diagnosed as congenital cataract (case group) and 172 normal children (control group) from May 2015 to May 2016. Genomic DNA extraction was performed using a QIAamp DNA blood mini kit. Polymerase chain reaction (PCR) products were genotyped using an ABI direct sequencer. Haplotype, allele, and genotype frequencies of CRYAA and CRYAB gene polymorphisms analyses were carried out using the SHEsis software. Logistic regression analysis was performed in order to analyze the risk factors for children suffering from congenital cataract.Presence of significant differences between the case and control groups' genotype and allele frequencies of CRYAA rs7278468 and CRYAB rs370803064/rs387907338. TA of CRYAB gene might increase congenital cataract risk in children, while GCG of CRYAA gene and GC of CRYAB gene might decrease congenital cataract risk in children. CRYAA rs7278468, CRYAB rs370803064/rs387907338 polymorphisms were significantly correlated to uncorrected visual acuity, best-corrected visual acuity, nystagmus, visual axis opacification, microcornea, lens opacity, posterior capsular thickening, and degrees of posterior capsule opacification after operation in children with congenital cataract. Logistic regression analysis revealed that the T allele of CRYAA rs7278468, A allele of CRYAB rs370803064, T allele of CRYAB rs387907338, family history, and TA haplotype of CRYAB gene were risk factors for children with congenital cataract.Our findings demonstrated that CRYAA rs7278468 and CRYAB rs370803064/rs387907338 are correlated with the risk and clinicopathological features of children suffering from congenital cataract.

SUBMITTER: Cui XJ

PROVIDER: S-EPMC5484201 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract.

Cui Xian-Jin XJ Lv Feng-Yan FY Li Feng-Hua FH Zeng Kun K

Medicine 20170601 25

<h4>Background</h4>The study aims to explore the correlations of the single nucleotide polymorphisms (SNPs) of CRYAA and CRYAB with the risk and clinicopathological features of children with congenital cataract.<h4>Methods</h4>The study enrolled 168 children diagnosed as congenital cataract (case group) and 172 normal children (control group) from May 2015 to May 2016. Genomic DNA extraction was performed using a QIAamp DNA blood mini kit. Polymerase chain reaction (PCR) products were genotyped ...[more]

PMID: 28640093

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Project description:BACKGROUND:Congenital cataract is the leading cause of blindness in children worldwide. Approximately half of all congenital cataracts have a genetic basis. Protein aggregation is the single most important factor in cataract formation. METHODS:A four-generation Chinese family diagnosed with autosomal dominant congenital cataracts and microphthalmia was recruited at the Shengjing Hospital of China Medical University. Genomic DNA was extracted from the peripheral blood of the participants. All coding exons and flanking regions of seven candidate genes (CRYAA, CRYBA4, CRYBB2, CRYGC, GJA8, MAF, and PITX3) were amplified and sequenced. Restriction fragment length polymorphism (RFLP) assays were performed to confirm the candidate causative variant, c.35G?>?T in the CRYAA gene. We constructed pcDNA3.1(+)-CRYAA expression plasmids containing either the wild-type or the R12L mutant alleles and respectively transfected them into HEK293T cells and into HeLa cells. Western blotting was performed to determine protein expression levels and protein solubility. Immunofluorescence was performed to determine protein sub-cellular localization. RESULTS:A heterozygous variant c.35G?>?T was identified in exon 1 of CRYAA, which resulted in a substitution of arginine to leucine at codon 12 (p.R12L). The nucleotide substitution c.35G?>?T was co-segregated with the disease phenotype in the family. The mutant R12L-CRYAA in HEK293T cells showed a significant increase in the expression level of the CRYAA protein compared with the wild-type cells. Moreover, a large amount of the mutant protein aggregated in the precipitate where the wild-type protein was not detected. Immunofluorescence studies showed that the overexpressed mutant CRYAA in HeLa cells formed large cytoplasmic aggregates and aggresomes. CONCLUSIONS:In summary, we described a case of human congenital cataract and microphthalmia caused by a novel mutation in the CRYAA gene, which substituted an arginine at position 12 in the N-terminal region of ?A-crystallin. The molecular mechanisms that underlie the pathogenesis of human congenital cataract may be characterized by the prominent effects of the p.R12L mutation on ?A-crystallin aggregation and solubility. Our study also expands the spectrum of known CRYAA mutations.

Dataset Information

Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract.

Publications

Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract.

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