A deletion mutation in the ?A1/A3 crystallin gene (CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family

Qi, Yanhua; Jia, Hepeng; Huang, Shangzhi; Lin, Hui Kuan; Gu, Jingjing; Su, Hong; Zhang, Tieying; Gao, Ya; Qu, Lijun; Li, Dandan; Liu, Ying

doi:10.1007/s00439-003-1049-7

Cited by 52 publications

(14 citation statements)

References 39 publications

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“…This mutation results in a semi-dominant nuclear cataract phenotype (Graw et al, 1999). There are five reports of human mutations in βA3/A1-crystallin, all with dominant or semi-dominant cataract phenotypes (Kannabiran et al, 1998;Bateman et al, 2000;Qi et al, 2004;Ferrini et al, 2004;Reddy et al, 2004). Two of the mutations are at the five prime (donor) splice site of intron 3.…”

Section: Resultsmentioning

confidence: 99%

“…This interval contained 49 genes identified through the reference sequence annotation database for the rat genome assembly, which we augmented by alignment with the mouse and human genomes. One of the genes was the βA3/A1-crystallin gene, which has been shown to cause congenital cataracts when mutated (Kannabiran et al, 1998;Bateman et al, 2000;Qi et al, 2004;Ferrini et al, 2004;Reddy et al, 2004;Graw et al, 1999). This gene was sequenced and the mutation was identified as a 27 base insertion in the 6th exon.…”

Section: Gene Candidate Selectionmentioning

confidence: 99%

“…Both polypeptides are affected by the Nuc1 mutation. Mutations in βA3/A1-crystallin are well known to cause cataract in both humans and mice (Kannabiran et al, 1998;Bateman et al, 2000;Qi et al, 2004;Ferrini et al, 2004;Reddy et al, 2004;Graw et al, 1999). In Nuc1 homozygotes, however, in addition to cataracts, severe retinal and other ocular abnormalities are apparent Hose et al, 2005;Zhang et al, 2005;Gehlbach et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Sinha

Klise

Sergeev

et al. 2008

Molecular and Cellular Neuroscience

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Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague-Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the βA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina.

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Section: Resultsmentioning

confidence: 99%

Section: Gene Candidate Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Sinha

Klise

Sergeev

et al. 2008

Molecular and Cellular Neuroscience

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“…Several deletion mutations have been identified in CRYBA1 gene 31, 32 and CRYBA1c.272_274delGAG has been widely reported 33–36 . Xu indicated that DeltaG91 mutation of CRYBA1altered protein-protein interaction between human lens betaA1-crystallins, and lead to protein insolubilization and contribute to cataracts 37 .…”

Section: Discussionmentioning

confidence: 99%

Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families

Zhai

et al. 2017

Sci Rep

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Congenital cataract is the most frequent inherited ocular disorder and the most leading cause of lifelong visual loss. The screening of pathogenic mutations can be very challenging in some cases, for congenital cataracts are clinically and genetically heterogeneous diseases. The aim of this study is to investigate the mutation spectrum and frequency of 54 cartaract-associated genes in 27 Chinese families with congenital cataracts. Variants in 54 cataract-associated genes were screened by targeted next-generation sequencing (NGS) and then validated by Sanger sequencing. We identified pathogenic variants in 62.96% (17/27) of families, and over 52.94% (9/17) of these variants were novel. Among them, three are splicing site mutations, four are nonsense mutations, seven are missense mutations, two are frame shift mutations and one is intronic mutation. This included identification of: complex ocular phenotypes due to two novel PAX6 mutations; progressive cortical cataract and lamellar cataract with lens subluxation due to two novel CRYGS mutations. Mutations were also found in rarely reported genes including CRYBA4, CRYBA2, BFSP1, VIM, HSF4, and EZR. Our study expands the mutation spectrum and frequency of genes responsible for congenital cataracts. Targeted next-generation sequencing in inherited congenital cataract patients provided significant diagnostic information.

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“…Genetic factors play an important role in the development of congenital cataracts, and hereditary congenital cataracts are inherited primarily in an autosomal dominant pattern. The identified genes involved in congenital cataracts include ten crystalline genes (αA-crystallin [ CRYAA ] [2], αB-crystallin [ CRYAB ] [3], βA1-crystallin [ CRYBA1 ] [4], βA4-crystallin [ CRYBA4 ] [5], βB1-crystallin [ CRYBB1 ] [6], βB2-crystallin [ CRYBB2 ] [7], βB3-crystallin [ CRYBB3 ] [8], γC-crystallin [ CRYGC ] [9], γD-crystallin [ CRYGD ] [10], and γS-crystallin [ CRYGS ] [11]), two cytoskeletal protein genes (beaded filament structural protein 2, phakinin [ BFSP2 ] [12] and beaded filament structural protein 1, filensin [ BFSP1 ] [13]), three transcription factor genes (heat shock transcription factor 4 [ HSF4 ] [14], Maf-like protein [ MAF ] [15], and paired-like homeodomain 3 [ PITX3 ] [16]), glucosaminyl (N-acetyl) transferase 2 ( GCNT2 ) [17], chromatin-modifying protein-4B ( CHMP4B ) [18], transmembrane protein 114 ( TMEM114 ) [19], and four membrane transport protein genes (major intrinsic protein of lens fiber [ MIP ] [20], lens intrinsic membrane protein 2 gene [ LIM2 ] [21], gap junction protein [alpha 8, GJA8 ] [22], and gap junction protein [alpha 3, GJA3 ] [23]). Congenital cataracts are characterized by high genetic heterogeneity and clinical heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

A Novel MIP Gene Mutation Analysis in a Chinese Family Affected with Congenital Progressive Punctate Cataract

et al. 2014

Self Cite

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Congenital cataracts are one of the leading causes of visual impairment and blindness in children, and genetic factors play an important role in their development. This study aimed to identify the genetic defects associated with autosomal dominant congenital progressive punctate cataracts in a Chinese family and to explore the potential pathogenesis. Detailed family history and clinical data were recorded, and all the family members’ blood samples were collected for DNA extraction. Linkage analysis was performed by microsatellite markers that are associated with punctate cataracts, and logarithm (base 10) of odds (LOD) scores were calculated using the LINKAGE program. Positive two-point LOD scores were obtained at markers D12S1622 (Zmax = 2.71 at θ = 0.0), D12S1724 (Zmax = 2.71 at θ = 0.0), and D12S90 (Zmax = 2.71 at θ = 0.0), which flank the major intrinsic protein of lens fiber (MIP) gene on chromosomal region 12q13. Direct sequencing of the encoding region of the MIP gene revealed a novel mutation (G>D) in exon 4 at nucleotide 644, which caused a substitution of glycine to aspartic acid at codon 215 (p.G215D) for the MIP protein. The mutation cosegregated with all patients with congenital progressive punctate cataracts, but it was absent in the healthy members. Bioinformatics analysis predicted that the mutation affects the function of the MIP protein. The wild type (WT) and G215D mutant of MIP were transfected with green fluorescent protein (GFP) into Hela cells separately, and it was found that the G215D mutant was aberrantly located in the cytoplasm instead of in the plasma membrane. In summary, our study presented genetic and functional evidence linking the new MIP mutation of G215D to autosomal dominant congenital cataracts, which adds to the list of MIP mutations linked to congenital progressive punctate cataracts.

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A deletion mutation in the ?A1/A3 crystallin gene (CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family

Cited by 52 publications

References 39 publications

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype–Phenotype Correlations in 27 Chinese Han Families

A Novel MIP Gene Mutation Analysis in a Chinese Family Affected with Congenital Progressive Punctate Cataract

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