Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urea-soluble and intrinsic membrane proteins from normal and galactose cataractous rat lenses were analyzed by SDS-PAGE. During cataract formation, MP22 increased whereas MP26 decreased almost to nil and MP24 emerged. However, the relative amount of MP18 remained essentially unchanged. These results suggested a conversion of MP26 to MP22 during cataract formation. We also observed the changes in the relative abundance of the polypeptides of the urea-soluble fraction with cataractogenesis.
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PMID:Changes of urea-soluble and intrinsic membrane proteins in rat lenses during the formation of galactose cataract. 147 76

Four genes encoding eye lens-specific proteins, potential candidate genes for congenital cataract (CC) mutations, were mapped in the mouse genome using a panel of somatic cell hybrids and DNAs from the EU-CIB (European Collaborative Interspecific Backcross). Two of them are lens fiber cell structural proteins: the Cryba1 locus encoding crystallinbetaA3/A1 maps to chromosome 11, 2.5 +/- 2.5 cM distal to D11Mit31, and the Crybb2 locus encoding crystallinbetaB2 maps to chromosome 5, 9.1 +/- 4.3 cM distal to D5Mit88. The other two genes encode lens-specific gap junction and integral membrane proteins, respectively: The Gja8 locus encoding gap juction membrane channel protein alpha8, also called connexin50 or MP70, maps to chromosome 3, 11.9 +/- 5.0 cM distal to D3Mit22, and the Lim2 locus encoding lens intrinsic membrane protein 2, also called MP19, maps to chromosome 7, 2.5 +/- 2.5 cM proximal to Ngfg. All four map positions, when compared with the corresponding positions in human, lie within known regions of conserved synteny between mouse and human chromosomes.
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PMID:Mapping of four mouse genes encoding eye lens-specific structural, gap junction, and integral membrane proteins: Cryba1 (crystallin beta A3/A1), Crybb2 (crystallin beta B2), Gja8 (MP70), and Lim2 (MP19). 866 93

Many types of inherited early onset cataract are known in both human and mouse. Here we describe the mapping of two novel dominant cataract loci in the mouse genome. Cataract and curly whiskers, Ccw, maps to Chromosome 4, 3.1 +/- 1.1 cM distal to the b (brown) locus. Total opacity 3, To3, maps to Chromosome 7, 7.1 +/- 1.8 cM proximal to p (pink-eyed dilution). The map positions of two other dominant cataract mutants have now been refined by three-point crosses. Nuclear and posterior polar cataract, Npp, maps to the central part of Chromosome 5, 1.4 +/- 0.5 cM distal to We (dominant spotting-extreme, an allele at the Kit locus), and Opaque secondary fiber cell junctions, Opj, maps to the proximal region of Chromosome 16, 9.1 +/- 1.5 cM distal to the marker md (mahoganoid). While there are no obvious candidate genes in the vicinity of the Ccw, Npp, and Opj mutations, To3 lies remarkably close to the recently mapped Lim2 locus, which encodes lens intrinsic membrane protein 2, also called MP19.
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PMID:Two new cataract loci, Ccw and To3, and further mapping of the Npp and Opj cataracts in the mouse. 881 11

In an inbred Iraqi Jewish family, we have studied three siblings with presenile cataract first noticed between the ages of 20 and 51 years and segregating in an autosomal recessive mode. Using microsatellite repeat markers in close proximity to 25 genes and loci previously associated with congenital cataracts in humans and mice, we identified five markers on chromosome 19q that cosegregated with the disease. Sequencing of LIM2, one of two candidate genes in this region, revealed a homozygous T-->G change resulting in a phenylalanine-to-valine substitution at position 105 of the protein. To our knowledge, this constitutes the first report, in humans, of cataract formation associated with a mutation in LIM2. Studies of late-onset single-gene cataracts may provide insight into the pathogenesis of the more common age-related cataracts.
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PMID:A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family. 1191 74

Mammalian ocular lens development results via a differentiation program that is highly regulated by tissue-specific transcription factors. Central to this is the terminal differentiation of fiber cells, which develop from epithelial cells on the anterior surface of the lens, accompanied by a change in cell shape and expression of structural proteins (such as membrane proteins MP19, MIP26, connexin 43, 46, and 50, cytoskeletal proteins CP49, CP115, and alpha, beta, and gamma crystallins), creating a transparent, refractive index gradient in the lens. Mutations in genes controlling eye development and in lens structural protein genes are associated with multiple ocular developmental disorders, including cataracts and other opacities of the lens. Here we show that heat shock transcription factor 4 (HSF4) expression in the developing lens is required for correct lens development and that inactivation of hsf4 leads to early postnatal cataract formation with primary effects specific to terminal fiber cell differentiation. These data suggest that HSF4 acts as a critical transcription factor for lens-specific target gene expression, in particular regulating the small 25 kDa heat shock protein that acts as a modifier for lens opacity and cataract development. Thus, HSF4 fulfills a central role in controlling spatial and temporal expression of genes critical for correct development and function of the lens.
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PMID:Unique contribution of heat shock transcription factor 4 in ocular lens development and fiber cell differentiation. 1559 27

Molecular characterization of chromosomal rearrangements is a powerful resource in identification of genes associated with monogenic disorders. We describe the molecular characterization of a balanced familial chromosomal translocation, t(16;22)(p13.3;q11.2), segregating with congenital lamellar cataract. This led to the discovery of a cluster of lens-derived expressed sequence tags (ESTs) close to the 16p13.3 breakpoint. This region harbors a locus associated with cataract and microphthalmia. Long-range PCR and 16p13.3 breakpoint sequencing identified genomic sequence in a human genome sequence gap, and allowed identification of a novel four-exon gene, designated TMEM114, which encodes a predicted protein of 223 amino acids. The breakpoint lies in the promoter region of TMEM114 and separates the gene from predicted eye-specific upstream transcription factor binding sites. There is sequence conservation among orthologs down to zebrafish. The protein is predicted to contain four transmembrane domains with homology to the lens intrinsic membrane protein, LIM2 (also known as MP20), in the PMP-22/EMP/MP20 family. TMEM114 mutation screening in 130 congenital cataract patients revealed missense mutations leading to the exchange of highly-conserved amino acids in the first extracellular domain of the protein (p.I35T, p.F106L) in two separate patients and their reportedly healthy sibling and mother, respectively. In the lens, Tmem114 shows expression in the lens epithelial cells extending into the transitional zone where early fiber differentiation occurs. Our findings implicate dysregulation of expression of this novel human gene, TMEM114, in mammalian cataract formation.
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PMID:Characterization of a familial t(16;22) balanced translocation associated with congenital cataract leads to identification of a novel gene, TMEM114, expressed in the lens and disrupted by the translocation. 1749 39

Primary cataracts (CAT) are characterized as any form of opacities of the eye lenses and are not accompanied by other diseases. CAT may impair vision depending on their size, location, and their state of progression. In order to investigate the cause of congenital or juvenile CAT in inbred Angolan lions kept in German zoos, we analyzed the genomic sequences of 4 crystalline genes CRYAA, CRYAB, CRYBB2, and CRYBB1. In addition, 10 CAT candidate genes (GJA3, LIM2, CRYGA, CRYGB, CRYGC, CRYGD CRYGS, BFSP2, CRYBA4, and CRYBB1) were analyzed using adjacent microsatellites. We identified 10 single nucleotide polymorphisms in the Angolan lion crystalline genes and 9 segregating microsatellites. Nonparametric and parametric linkage analyses did not reveal any linkage between one of the analyzed markers and CAT. So, we concluded that these genes can be excluded as causative for the familial primary cataract phenotype in these Angolan lions.
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PMID:Development of feline microsatellites and SNPs for evaluating primary cataract candidate genes as cause for cataract in Angolan lions (Panthera leo bleyenberghi). 2042 16

Congenital cataract is the common cause of visual disability in children. Inherited isolated (non-syndromic) cataract represents one third of cases. Currently, at least 22 specific genes associated with isolated inherited cataract have been identified: ten crystallin genes: CRYAA, CRYAB, CRYBA1/A3, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS; 4 membrane protein genes: GJA3, GJA8, MIP, LIM2; three growth and transcription factor genes: PITX3, MAF, HSF4; two cytoskeletal protein gene: BSFP1, BSFP2; chromatin modifying protein-4B gene: CHMP4B, EPHA2 and NHS, it is likely that more genes remain to be discovered. Some of the genes have been studied for their function by expression in cells or/and by knock-out animal models. The increasing availability of more detailed information about their functions makes it possible to understand the pathophysiology of congenital cataracts.
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PMID:[Progress in pathogenic genes and their functions of congenital cataract]. 2045 Jun 75

Congenital cataract is a highly heterogeneous disorder at both the genetic and the clinical-phenotypic levels. A unique cataract was observed in a 4-generation Chinese family, which was characterized by autosomal dominant inheritance and late-onset. Mutations in the 13 known genes (CRYAA, CRYAB, CRYBB1, CRYBB2, CRYGC, CRYBA1/A3, CRYGD, Connexin50, Connexin46, intrinsic membrane protein LIM2, cytoskeletal protein BFSP2, the major intrinsic protein-MIP and the heat shock factor HSF4) have previously been demonstrated to be the frequent reason for isolated congenital cataracts, but the exact molecular basis and underlying mechanisms of congenital cataract still remain unclear. This study was designed to find whether these 13 genes developed any mutation in the family members and to identify the disease-causing gene. Polymerase chain reaction (PCR) and direct DNA sequence analysis were carried out to detect the 13 genes. The results showed that no mutation causing amino acid alternations was found in these potential candidate genes among all patients in the family, and only several single-nucleotide polymorphisms (SNPs) were identified. A transitional mutation in the fourth intron of CRYBB2 and some silent mutations in the first exon of BFSP2 and CRYGD were found in the cataract family, but further study showed that these mutations could also be found in normal controls. It was concluded that some unidentified genes may underlie the occurrence of late-onset cataract in this family. A genome-wide screening will be carried out in the next study.
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PMID:Molecular genetic analysis of autosomal dominant late-onset cataract in a Chinese Family. 2118 74

Congenital cataract is a crystallin severe blinding disease and genetic factors in disease development are important. Crystallin growth is under a combination of genes and their products in time and space to complete the coordination role of the guidance. Congenital cataract-related genes, included crystallin protein gene (CRYAA, CRYAB, CRYBA1/A3, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS), gap junction channel protein gene (GJA1, GJA3, GJA8), membrane protein gene (GJA3, GJA8, MIP, LIM2), cytoskeletal protein gene (BF-SP2), transcription factor genes (HSF4, MAF, PITX3, PAX6), ferritin light chain gene (FTL), fibroblast growth factor (FGF) and so on. Currently, there are about 39 genetic loci isolated to which primary cataracts have been mapped, although the number is constantly increasing and depends to some extent on definition. We summarized the recent advances on epidemiology and genetic locations of congenital cataract in this review.
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PMID:Epidemiology and molecular genetics of congenital cataracts. 2255 94


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