Novel β-Crystallin Gene Mutations in Chinese Families With Nuclear Cataracts

Wang, Kai Jie; Wang, Bin Bin; Zhang, Fengju; Zhao, Yanyan; Ma, Xu; Zhu, Si Quan

doi:10.1001/archophthalmol.2011.11

Cited by 27 publications

(24 citation statements)

References 16 publications

(17 reference statements)

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“…Hansen et al selected 28 Danish families with hereditary congenital cataracts to screen 17 genes and found that mutations in genes encoding crystallins and connexins accounted for 53.5% [7]. Other studies have screened only a few genes in different populations and all of their results showed that the mutation frequencies were no more than 20% [7]–[10],[12],[22]. In our previous study, we screened all of the 12 genes encoding crystallins and connexins in 25 Chinese families, and 40% of the families were found to carry mutations [13].…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing of 18 Chinese Families with Congenital Cataracts: A New Sight of the NHS Gene

Sun

Xiao

et al. 2014

PLoS ONE

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PurposeThe aim of this study was to investigate the mutation spectrum and frequency of 34 known genes in 18 Chinese families with congenital cataracts.MethodsGenomic DNA and clinical data was collected from 18 families with congenital cataracts. Variations in 34 cataract-associated genes were screened by whole exome sequencing and then validated by Sanger sequencing.ResultsEleven candidate variants in seven of the 34 genes were detected by exome sequencing and then confirmed by Sanger sequencing, including two variants predicted to be benign and the other pathogenic mutations. The nine mutations were present in 9 of the 18 (50%) families with congenital cataracts. Of the four families with mutations in the X-linked NHS gene, no other abnormalities were recorded except for cataract, in which a pseudo-dominant inheritance form was suggested, as female carriers also had different forms of cataracts.ConclusionThis study expands the mutation spectrum and frequency of genes responsible for congenital cataract. Mutation in NHS is a common cause of nonsyndromic congenital cataract with pseudo-autosomal dominant inheritance. Combined with our previous studies, a genetic basis could be identified in 67.6% of families with congenital cataracts in our case series, in which mutations in genes encoding crystallins, genes encoding connexins, and NHS are responsible for 29.4%, 14.7%, and 11.8% of families, respectively. Our results suggest that mutations in NHS are the common cause of congenital cataract, both syndromic and nonsyndromic.

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Section: Discussionmentioning

confidence: 99%

Exome Sequencing of 18 Chinese Families with Congenital Cataracts: A New Sight of the NHS Gene

Sun

Xiao

et al. 2014

PLoS ONE

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“…The isolated DNA was amplified by polymerase chain reaction (PCR) for the exons and their flanking regions using previously published primers sequences with modification for exon 6 of the CRYBB2 [10], [12], [19]. Primers for exon 6 of the CRYBB2 were as follows: forward; 5′-AGAAAGCAGAGGCTCAGTGC -3′ and reverse; 5′-GGAGATCAAAGACCCACAGC-3′.…”

Section: Methodsmentioning

confidence: 99%

A Missense Mutation in CRYBB2 Leads to Progressive Congenital Membranous Cataract by Impacting the Solubility and Function of βB2-Crystallin

Chen

et al. 2013

PLoS ONE

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Congenital cataract is a major cause of visual impairment and childhood blindness. The solubility and stability of crystallin proteins play critical roles in maintaining the optical transparency of the lens during the life span. Previous studies have shown that approximately 8.3%∼25% of congenital cataracts are inherited, and mutations in crystallins are the most common. In this study, we attempted to identify the genetic defect in a four-generation family affected with congenital cataracts. The congenital cataract phenotype of this four-generation family was identified as membranous cataract by slit-lamp photography. Mutation screening of the candidate genes detected a heterozygous c.465G→C change in the exon6 of the βB2-crystallin gene (CRYBB2) in all family members affected with cataracts, resulting in the substitution of a highly conserved Tryptophan to Cystine (p.W151C). The mutation was confirmed by restriction fragment length polymorphism (RFLP) analysis and found that the transition resulted in the absence of a BslI restriction site in the affected members of the pedigree. The outcome of PolyPhen-2 and SIFT analysis predicted that this W151C mutation would probably damage to the structure and function of βB2-crystallin. Wild type (wt) and W151C mutant βB2-crystallin were expressed in human lens epithelial cells (HLECs), and the fluorescence results showed that Wt-βB2-crystallin was evenly distributed throughout the cells, whereas approximately 34.7% of cells transfected with the W151C mutant βB2-crystallin formed intracellular aggregates. Taken together, these data suggest that the missense mutation in CRYBB2 gene leads to progressive congenital membranous cataract by impacting the solubility and function of βB2-crystallin.

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“…Early childhood surgery was required in some cases, but no comments were made in the report regarding cycloplegic refractions. The third and fourth reported CRYBB1 mutations, p.S228P and p.Q223X, were associated with central nuclear cataract in Chinese families 17 19. Details regarding need for surgery, cycloplegic refractions and whether or not the opacities were pulverulent were not provided, although at least one unoperated child with p.S228P CRYBB1 mutation had nystagmus17 and older individuals with p.Q223X CRYBB1 mutation were described as having denser lens opacities 19.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular analysis of children with central pulverulent cataract from the Arabian Peninsula

et al. 2012

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Central pulverulent cataract in this consanguineous population does not significantly impact visual acuity during early childhood, can be associated with significant ametropias (with amblyopia and/or strabismus) and is specific for a homozygous CRYBB1 founder mutation. Primary management in children is typically spectacle correction based on cycloplegic retinoscopy to treat significant refractive error rather than paediatric cataract surgery.

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Novel β-Crystallin Gene Mutations in Chinese Families With Nuclear Cataracts

Cited by 27 publications

References 16 publications

Exome Sequencing of 18 Chinese Families with Congenital Cataracts: A New Sight of the NHS Gene

Exome Sequencing of 18 Chinese Families with Congenital Cataracts: A New Sight of the NHS Gene

A Missense Mutation in CRYBB2 Leads to Progressive Congenital Membranous Cataract by Impacting the Solubility and Function of βB2-Crystallin

Clinical and molecular analysis of children with central pulverulent cataract from the Arabian Peninsula

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