Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Wang, Zhenyu; Huang, Chen; Sun, Yu; Lv, Huibin; Zhang, Mingzhou; Li, Xuemin

doi:10.1101/367516

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…This information indicates that the coralliform phenotype and the CRYGD gene are closely related. Our results support the idea that virulence genes and lens morphology are related 23 24 25 26 27 28 29 . Results of biophysical analysis have shown that the P24T mutant protein has a significantly lower solubility than wild-type human γD crystalline 30 31 .…”

Section: Discussionsupporting

confidence: 88%

Novel mutations in CRYGD are associated with congenital cataracts in Chinese families

Yang

Chen

Zhang

et al. 2016

Sci Rep

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Congenital cataract disease is a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the genetic defects and to investigate the relationships between disease-causing genes and lens morphology in congenital cataracts. Patients were given a physical examination, and their blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the following candidate genes: CRYGC, CRYGD, CRYGS, GJA8, GJA3 and CRYAA. Mutational analysis of CRYGD identified a recurrent (p.P24T) mutation in two unrelated families with congenital coralliform cataracts and three novel (p.Q101X, p.E104fsX4 and p.E135X) mutations in three families with congenital nuclear cataracts. The p.E135X mutation is a de novo mutation. Haplotype analysis showed patients inherited the same CRYGD allele originated from father. The p.E135X mutation seen in two siblings suggests a mechanism of gonadal mosaicism in the father.

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Section: Discussionsupporting

confidence: 88%

Novel mutations in CRYGD are associated with congenital cataracts in Chinese families

Yang

Chen

Zhang

et al. 2016

Sci Rep

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“…Among them, BFSP2 (phakinin or CP49) and BFSP1 ( lensin) assemble into lens-speci c beaded intermediate laments, which are one of the main cytoskeletal structures in the lens ber [38,39] . BFSP1 and BFSP2 have been con rmed to be genes associated with autosomal dominant cataracts [40,41] . Moreover, the absence of BFSP2 or BFSP1 causes the disappearance of beaded intermediate laments and changes the morphology of lens ber cells [42] .…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na 2 Se0 3 -induced Sprague Dawley rat cataract model

Fang

Yue

et al. 2023

Preprint

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Background A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression. Methods cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed the high-throughput RNA sequencing technology to identify the mRNA and miRNA expression profiles of the capsular membrane of the lens from Na2Se03-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein-protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes’ targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape. Result In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. 47 DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological process. A protein-protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which confirming by qRT-PCR analysis. Conclusion We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2Se03-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.

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“…In current study, a wide spectrum cataract gene panel screening was performed in two probands from two separate Chinese congenital cataract pedigrees with autosomal dominant inheritance, a heterozygous variant of CRYGD gene in exon 2 (70C>A, P24T) was identified as a disease-causing gene as this mutation was co-segregated with the disease within two families. Previous studies reported that ten mutated variants in CRYGD gene, including P24T, and others such as R15S, R15C, P24S, R37S, R59H, G61C, and Y134X [18][19][20] , manifested with vast phenotypic variations as a result of genotypic heterogeneity [18,[21][22][23][24][25][26][27][28][29] . As examples, Y56X, Y134C, and R58H were reported to be related with nuclear cataract, lamellar cataract and aculeiform/coral-like cataract, respectively [22,[30][31] .…”

Section: Clinical Evaluationmentioning

confidence: 99%

A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees

Cai

Wang

et al. 2021

Int J Ophthalmol

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AIM: To investigate the causal gene mutation and clinical characteristics for two Chinese families with autosomal dominant congenital coralliform cataract. METHODS: Two Chinese pedigrees with congenital cataract were investigated. Routine ophthalmic examinations were performed on all patients and non-affected family members. Peripheral blood samples were collected, and the genomic DNAs were extracted. The coding regions of proband’s DNAs were analyzed with cataract gene panel. The identified mutation was amplified by polymerase chain reaction, and automated sequencing was performed in other members of two families to verify whether the mutated gene was co-segregated with the disease. RESULTS: Congenital coralliform cataract was inherited in an autosomal dominant mode in both pedigrees. For each family, more than half of the family members were affected. All patients presented with severe visual impairment after birth as a result of bilateral symmetric coralliform lens opacification. An exact the same defect in the same gene, a heterozygous mutation of c.70C>A (p. P24T) in exon 2 of γD-crystallin gene, was detected in both probands from each family. Sanger sequencing analysis demonstrated that the mutated CRYGD was co-segregated in these two families. CONCLUSION: A c.70C>A (p. P24T) variant in CRYGD gene was reconfirmed to be the causal gene in two Chinese pedigrees. It is known that mutated CRYGD caused most of the congenital coralliform cataracts, suggesting that the CRYGD gene is associated with coralliform congenital cataract.

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Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Cited by 3 publications

References 24 publications

Novel mutations in CRYGD are associated with congenital cataracts in Chinese families

Novel mutations in CRYGD are associated with congenital cataracts in Chinese families

Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na 2 Se0 3 -induced Sprague Dawley rat cataract model

A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees

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