A novel frameshift mutation in CX46 associated with hereditary dominant cataracts in a Chinese family

Cui, Xiukun; Zhu, Keke; Zhou, Zheng; Wan, Simin; Dong, Yi; Wang, Xuan‐Ce; Li, Jing; Zhang, Jing; Mu, Hongmei; Lei, Qin; Hu, Yanzhong

doi:10.18240/ijo.2017.05.04

Cited by 3 publications

(4 citation statements)

References 25 publications

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“…In Family 2, frameshift S385Efs*83 in GJA3 resulted from a guanine insertion that introduced a premature translation stop codon located in the COOH-terminus, which may interfere with the folding of the whole protein and resulted in cataract. This insertion mutation (c.1152_1153insG) is similar to the three mutations (c.1137dupC, c.1189dupG, c.1200dupC) reported previously [25–27], thus providing further evidence that the GJA3 C-terminal domain plays an essential role in physiological function of the gene, and further expanding the mutation spectrum of GJA3 in association with congenital cataract.…”

Section: Discussionsupporting

confidence: 82%

Novel mutations identified in Chinese families with autosomal dominant congenital cataracts by targeted next-generation sequencing

Zhang

Cao

et al. 2019

BMC Med Genet

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BackgroundCongenital cataract is a clinically and genetically heterogeneous visual impairment. The aim of this study was to identify causative mutations in five unrelated Chinese families diagnosed with congenital cataracts.MethodsDetailed family history and clinical data were collected, and ophthalmological examinations were performed using slit-lamp photography. Genomic DNA was extracted from peripheral blood of all available members. Thirty-eight genes associated with cataract were captured and sequenced in 5 typical nonsyndromic congenital cataract probands by targeted next-generation sequencing (NGS), and the results were confirmed by Sanger sequencing. Bioinformatics analysis was performed to predict the functional effect of mutant genes.ResultsResults from the DNA sequencing revealed five potential causative mutations: c.154 T > C(p.F52 L) in GJA8 of Family 1, c.1152_1153insG(p.S385Efs*83) in GJA3 of Family 2, c.1804 G > C(p.G602R) in BFSP1 of Family 3, c.1532C > T(p.T511 M) in EPHA2 of Family 4 and c.356G > A(p.R119H) in HSF4 of Family 5. These mutations co-segregated with all affected individuals in the families and were not found in unaffected family members nor in 50 controls. Bioinformatics analysis from several prediction tools supported the possible pathogenicity of these mutations.ConclusionsIn this study, we identified five novel mutations (c.154 T > C in GJA8, c.1152_1153insG in GJA3, c.1804G > C in BFSP1, c.1532C > T in EPHA2, c.356G > A in HSF4) in five Chinese families with hereditary cataracts, respectively. NGS can be used as an effective tool for molecular diagnosis of genetically heterogeneous disorders such as congenital cataract, and the results can provide more effective clinical diagnosis and genetic counseling for the five families.

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Section: Discussionsupporting

confidence: 82%

Novel mutations identified in Chinese families with autosomal dominant congenital cataracts by targeted next-generation sequencing

Zhang

Cao

et al. 2019

BMC Med Genet

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“…These findings suggested that rs2162679 was only associated with mild and moderate myopia rather than high or extreme myopia. To date, six MYPs (MYP6-10 and MYP14) have been discovered and mapped in populations with mild and moderate myopia (Cui et al, 2017). Baltimore et al mapped a myopia-related region in chromosome 1p36 in an Ashkenazi Jewish population with a mean SE of −3.46 D (Wojciechowski et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Myopia is a complex disease affected by both genetic and environmental factors, whose etiology and pathogenesis remain unclear (Morgan et al, 2018). Previous studies have identified 26 myopia-related loci (MYP1-MYP26 ) through various methods, such as family-based linkage analyses, genome-wide association studies, and whole exon sequencing studies (Cui et al, 2017;Guo et al, 2015;Wang et al, 2017;Xiao et al, 2016). Some candidate genes are associated with high myopia, while some are related to moderate myopia (Zhang, 2015).…”

Section: Introductionmentioning

confidence: 99%

Association of IGF1 single-nucleotide polymorphisms with myopia in Chinese children

Cheng

Wang

Xiong

et al. 2020

PeerJ

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Purpose To investigate the association between insulin-like growth factor 1 (IGF1) single-nucleotide polymorphisms (SNPs) and myopia in a young Chinese population. Methods A total of 654 Chinese children aged 6–13 years from one primary school participated in our study and underwent a series of comprehensive ocular examinations, including cycloplegic refraction and measurements of axial length. Myopia was defined as a spherical equivalence (SE) ≤ −0.5 D in the worse eye. In total, six tagging SNPs of IGF1 were genotyped using the PCR-LDR (Polymerase Chain Reaction-Ligation Detection Reaction) method. We tested four different genetic modes (the allele, dominant, recessive, and additive models) of these SNPs and used multivariate logistic regression to calculate the effect of SNPs on myopia. In addition, we conducted a haplotype analysis with a variable-sized slide-window strategy. Results Overall, 281 myopic children and 373 non-myopic controls were included in the analysis. The SNP rs2162679 showed a statistical difference between the two groups in both the allele (p = 0.0474) and additive (p = 0.0497) models. After adjusting for age and gender, children with the genotype AA in the SNP rs2162679 had a higher risk of myopia than those with the genotype GG (OR = 2.219, 95% CI [1.218–4.039], p = 0.009). All haplotypes that varied significantly between the two groups contained the SNP rs2162679, and the four-SNP window rs5742653–rs2162679 had the lowest p value (Chi square = 5.768, p = 0.0163). However, after permutation tests, none of the associations remained statistically significant. Conclusion The SNP rs2162679 in IGF1 was associated with myopia in a young Chinese population. The G allele in the SNP rs2162679 may protect against myopia.

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“…Most congenital cataracts are autosomal dominant; however, autosomal recessive and X-linked patterns have also been reported (Stephan et al, 1999). To date, approximately 28 genes have been identified to be associated with congenital cataracts; approximately 50% of the disease-causing mutations belong to the crystallin family and these gene mutations impair lens development at different stages (Cui et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Increased hydrophobicity of CRYGD p.(Ala159ProfsTer9): Suspected cause of congenital cataracts in a large Chinese family

Lin

Jin

Chen

et al. 2020

Molec Gen & Gen Med

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Congenital cataracts (complete or partial lens opacification) are the leading cause of visual impairment in early childhood. In general, a cataract is formed due to the aggregation of lens proteins, and it clinically presents as the clouding of the lens, disrupting the flow of light to the retina, thereby causing decreased clarity, dull color contrast, and impaired vision (Michael & Bron, 2011). The prevalence of cataracts is approximately 1-6 per 10,000 live births (Roshan et al., 2010),

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A novel frameshift mutation in CX46 associated with hereditary dominant cataracts in a Chinese family

Abstract: The insertion of cytosine at position 1195 of CX46 cDNA is a novel mutation site that is associated with the autosomal dominant cataracts in this Chinese family. The C-terminal frameshift mutation is involved in regulating CX46 protein expression.

Cited by 3 publications

References 25 publications

Novel mutations identified in Chinese families with autosomal dominant congenital cataracts by targeted next-generation sequencing

Novel mutations identified in Chinese families with autosomal dominant congenital cataracts by targeted next-generation sequencing

Association of IGF1 single-nucleotide polymorphisms with myopia in Chinese children

Increased hydrophobicity of CRYGD p.(Ala159ProfsTer9): Suspected cause of congenital cataracts in a large Chinese family

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