A CRYGC gene mutation associated with autosomal dominant pulverulent cataract

González-Huerta, Luz María; Messina-Baas, Olga; Urueta, Héctor; Toral-López, Jaime; Cuevas-Covarrubias, Sergio A.

doi:10.1016/j.gene.2013.07.044

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…The high levels of these proteins in mature lens fibers play an important role in establishing and maintaining the proper optical properties of the lenses. Mutations of γ-crystallins are associated with congenital cataracts in humans and in mice. − It was reported that the down-regulation of γ-S-crystallin expression was a potential mechanism for cataract formation in mice that lack functional Hsf4 . Furthermore, loss of γ-D-crystallin due to mutation in start codon caused cataract in rat .…”

Section: Discussionmentioning

confidence: 99%

Newborn Mouse Lens Proteome and Its Alteration by Lysine 6 Mutant Ubiquitin

et al. 2014

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Ubiquitin is a tag that often initiates degradation of proteins by the proteasome in the ubiquitin proteasome system. Targeted expression of K6W mutant ubiquitin (K6W-Ub) in the lens results in defects in lens development and cataract formation, suggesting critical functions for ubiquitin in lens. To study the developmental processes that require intact ubiquitin, we executed the most extensive characterization of the lens proteome to date. We quantified lens protein expression changes in multiple replicate pools of P1 wild-type and K6W-Ub-expressing mouse lenses. Lens proteins were digested with trypsin, peptides were separated using strong cation exchange and reversed-phase liquid chromatography, and tandem mass (MS/MS) spectra were collected with a linear ion trap. Transgenic mice that expressed low levels of K6W-Ub (low expressers) had normal, clear lenses at birth, whereas the lenses that expressed high levels of K6W-Ub (higher expressers) had abnormal lenses and cataracts at birth. A total of 2052 proteins were identified, of which 996 were reliably quantified and compared between wild-type and K6W-Ub transgenic mice. Consistent with a delayed developmental program, fiber-cell-specific proteins, such as γ-crystallins (γA, γB, γC, and γE), were down-regulated in K6W-Ub higher expressers. Up-regulated proteins were involved in energy metabolism, signal transduction, and proteolysis. The K6W-Ub low expressers exhibited delayed onset and milder cataract consistent with smaller changes in protein expression. Because lens protein expression changes occurred prior to lens morphological abnormalities and cataract formation in K6W-Ub low expressers, it appears that expression of K6W-Ub sets in motion a process of altered protein expression that results in developmental defects and cataract.

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Section: Discussionmentioning

confidence: 99%

Newborn Mouse Lens Proteome and Its Alteration by Lysine 6 Mutant Ubiquitin

et al. 2014

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“…17 Exon 2c.143G>AR48HADpulverulent congenital cataractin a Mexico familyGonzález-Huerta et al . 14 Exon 2c.157_161dupGCGGCQ55VfsX50ADcataractin a USA familyReis et al . 20 Exon 2c.193delGD65TfsX38ADNuclear cataractin a Chinese familyThis studyExon 3c.327C>AC109XADNuclear cataractin a Chinese familyYao et al .…”

Section: Discussionmentioning

confidence: 99%

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

Zhong

Han

et al. 2017

Sci Rep

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Congenital cataract (CC), responsible for about one-third of blindness in infants, is a major cause of vision loss in children worldwide. 10–25% of CC cases are attributed to genetic causes and CC is a clinically and genetically highly heterogeneous lens disorder in children. Autosomal dominant (AD) inheritance is the most commonly pattern. 195 unrelated non-syndromic ADCC families in this study are recruited from 15 provinces of China. Sanger sequencing approach followed by intra-familial co-segregation, in Silico analyses and interpretation of the variations according to the published guidelines of American College of Medical Genetics (ACMG), were employed to determine the genetic defects. Two mutations (p.Tyr139X and p.Ser166Phe) identified in two unrelated families were associated with their congenital nuclear cataracts and microcornea respectively, which are also reported previously. Six novel CRYGC mutations (p.Asp65ThrfsX38, p.Arg142GlyfsX5, p.Arg142AlafsX22, p.Tyr144X, p.Arg169X, and p.Tyr46Asp) were identified in other six families with congenital nuclear cataracts, respectively. Mutations in the CRYGC were responsible for 4.1% Chinese ADCC families in our cohort. Our results expand the spectrum of CRYGC mutations as well as their associated phenotypes.

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“…[13,19] Currently, over 40 loci have been mapped in congenital cataract development. [3] However, the mechanism of CRYAA and CRYAB mutations leading to congenital cataract remains unclear. The present study tried to investigate the effects of mutations on loci rs7278468, rs3761382, and rs13053109 on the CRYAA gene and rs370803064 and rs387907338 on the CRYAB gene on risks of pediatric congenital cataract.…”

Section: Discussionmentioning

confidence: 99%

“…[2] Congenital cataract prevalence is estimated to range from 0.6 to 6 per 10,000 live births, with an incidence rate of about 2.2 to 2.49 in every 10,000 live births, and an approximate 40% cases with congenital cataract are reported to be inherited in isolation or due to ocular syndrome or abnormalities. [3] Nearly a-third of congenital cataract cases are familial with an autosomal dominant or recessive inheritance. [4] Despite the remarkable improvements in the clinical cataract management and updated information of lens structure and function, the correlations among cataract morphology, etiology, and mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[13] Currently, over 40 loci have been mapped in congenital cataract development. [3] Our study targets to elucidate the effects of mutations on loci rs7278468, rs3761382, and rs13053109 of CRYAA and rs370803064 and rs387907338 of CRYAB on risks of pediatric congenital cataract to provide more genetic information on the cause of congenital cataract.…”

Section: Introductionmentioning

confidence: 99%

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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

Lv²,

et al. 2017

Medicine

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Background: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.Methods: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.Results: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.Conclusion:Our findings demonstrated that CRYAA rs7278468 and CRYAB rs370803064/rs387907338 are correlated with the risk and clinicopathological features of children suffering from congenital cataract.

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A CRYGC gene mutation associated with autosomal dominant pulverulent cataract

Cited by 6 publications

References 24 publications

Newborn Mouse Lens Proteome and Its Alteration by Lysine 6 Mutant Ubiquitin

Newborn Mouse Lens Proteome and Its Alteration by Lysine 6 Mutant Ubiquitin

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

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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