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)

In mammalian cells, cellular iron homeostasis is maintained by the co-ordinated regulation of transferrin receptor and ferritin synthesis that occurs at the translational level. This regulation is mediated by iron-responsive elements (IREs) that are found within the untranslated regions (UTRs) of mRNA and by cytoplasmic mRNA-binding proteins, known as iron regulatory proteins (IRPs). When cellular iron is scarce, IRPs are available for binding the 5' IRE of ferritin mRNA, initiation of translation is prevented and ferritin synthesis is inhibited. By contrast, the presence of abundant intracellular iron prevents binding of the IRPs to the 5' IRE and allows efficient mRNA translation to proceed. Hereditary hyperferritinaemia/cataract syndrome (HHCS) arises as a result of various point mutations or deletions within a protein binding sequence in the 5'-UTR of the L-ferritin mRNA, which results in increased efficiency of L-ferritin translation. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. This exemplifies a new paradigm in which mutations in mRNA cis-acting elements may be responsible for phenotypic variability in disease states.
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PMID:Hereditary hyperferritinaemia/ cataract syndrome. 1240 13

A cross-sectional ophthalmological survey to determine the ocular health in Nigerian industries was undertaken in four randomly selected industrial establishments in Enugu State of Nigeria. The industrial establishments studied were the cement factory, coal mine, saw mill and iron/steel works where motor spare parts are fabricated. Of the 646 workers, 184 (28.5%) had a history of industrial accidents, 81 (12.5%) of which affected the eye. Eye injury was most commonly caused by metal chips, cement dust, fragments of wood, pieces of coal stone and welders' arc rays all of which could be prevented by wearing appropriate protective eye coverings. Contusion injury was the most common type of injury reported. Eye accident rate varied from factory to factory as also did the wearing of protective eye devices. overall, the percentage of workers using protective eye cover was 16.7% but there was a significant difference between the factories in this respect, protective eye wear being more often used in factories with higher eye accident rates. A total of 646 technical workers had detailed ophthalmological examination. The types and frequencies ofvisual disorders seen as well as the nature and causes of eye injuries were determined. Five hundred and twenty-eight workers (81.7%) had eye disorders. Presbyopla was responsible for 203 (31.4%) of these disorders while 169 (26.2%) were refractive errors. Of the others, pterygium and pingueculum together numbered 179 (27.7%) while cataract was found in 79 (12.2%) subjects. The results showed a high frequency of eye injuries among industrial workers and a low level of use of protective eye cover while at work. It is recommended that legislation requiring the use of protective devices in high-risk industries should be vigorously enforced to improve the eye health of Nigerian industrial workers.
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PMID:Eye health of industrial workers in Southeastern Nigeria. 1240 36

Iron overload may predominantly involve parenchymal or reticuloendothelial cells, the prototype of parenchymal iron overload being HFE-related genetic haemochromatosis. We studied a family with autosomal dominant hyperferritinaemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. Analysis of L and H ferritin genes excluded mutations responsible for hereditary hyperferritinaemia/cataract syndrome or similar translational disorders. Sequence analysis of the ferroportin gene (SLC11A3) in four individuals with hyperferritinaemia singled out a three base pair deletion in a region that contains four TTG repeats. This mutation removes a TTG unit from 780 to 791, and predicts the loss of one of three sequential valine residues 160-162. Denaturing high performance liquid chromatography can be used for its detection. SLC11A3 polymorphism analysis indicates that this probably represents a recurrent mutation due to slippage mispairing. Affected individuals may show marginally low serum iron and transferrin saturation, and young women may have marginally low haemoglobin concentration levels. Serum ferritin levels are directly related to age, but are 10-20 times higher than normal. Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias.
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PMID:Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3). 1240 98

Ferritin, composed of H-subunits and L-subunits, plays important roles in iron storage and in the control of intracellular iron distribution. Synthesis of both subunits is controlled by common cytoplasmic proteins, iron regulatory proteins (IRP-1 and IRP-2) that bind to the iron-responsive element (IRE) in the 5'-untranslated region of ferritin messenger RNA (mRNA). When intracellular iron is scarce, IRPs display IRE binding to suppress translation of mRNA. When cellular iron is abundant, IRPs become inactivated (IRP-1) or degraded (IRP-2). In the last few years, IRE mutations that cause disorders due to dysregulation of ferritin subunit synthesis have been identified. Hereditary hyperferritinemia-cataract syndrome is associated with point mutations or deletions in the IRE of L-subunit mRNA and is characterized by constitutively increased synthesis of L-subunits but is unrelated to iron overload. A single-point mutation in the IRE of H-subunit mRNA in members of a family affected with dominantly inherited iron overload has been reported. This review summarizes the current understanding of the translational disorders caused by IRE mutations in ferritin mRNA.
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PMID:Recent advance in molecular iron metabolism: translational disorders of ferritin. 1241 30

Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder characterized by bilateral cataracts and increased serum L-ferritin, in the absence of iron overload. Under physiological conditions, ferritin synthesis is finely regulated at the translational level by iron availability. This regulation is achieved by the high-affinity interaction between cytoplasmic mRNA-binding proteins (iron regulatory proteins, IRPs), and mRNA stem-loop structures, known as iron responsive elements (IREs), located in the untranslated regions (UTRs) of the mRNAs. A single IRE is located on the 5' UTR of a series of genes involved in iron metabolism, like L-ferritin, and the binding IRE-IRPs represses these genes translation. The deregulation of ferritin production responsible of HHCS is caused by heterogeneous mutations in the iron regulatory element (IRE) of L-ferritin that interfere with the binding of iron regulatory proteins, disrupting the negative control of L-ferritin synthesis and causing the constitutive up-regulation of ferritin L-chains. The HHCS families originate from different countries of Europe and North America, suggesting that HHCS may be distributed widely throughout the world and not sporadic, whereas its prevalence remains to be established. The lens seems to be particularly sensitive to the increased amount of L-ferritin and the alteration of the proteic equilibrium in this tissue can be responsible of the cataract. In spite of the elucidation of the genetic basis, the genotype phenotype correlation is not clear. Recently, a study based on the thermo-denaturation profile and dissociation constant of the IRE-IRP complex performed for several mutated IREs has provided evidence for a possible correlation between heterogeneous IRE mutations and serum ferritin levels. On the other hand, the in vivo relevance of these conclusions has not been determined completely. A clinical variability among subjects sharing the same mutation, whether they belonged to the same family or not, has also been demonstrated. These findings suggest that, besides the L-ferritin IRE genotype, additional factors are likely to modulate the lens involvement and the rate of progression to severe cataract in HHCS patients.
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PMID:Pathogenesis of hyperferritinemia cataract syndrome. 1254 47

Two teenaged girls had orthokeratology to correct myopia. The postoperative development of corneal iron rings in both eyes was disclosed by a biomicroscopic examination at 3 months in 1 patient and 5 months in the other. The location of the corneal iron rings coincided with the fitting curve of the reverse-geometry rigid contact lens, suggesting that the rings might have developed from tear pooling.
J Cataract Refract Surg 2003 Mar
PMID:Corneal iron ring associated with orthokeratology. 1266 37

The purpose of the study was to examine the zinc and iron content of human lenses in different types of cataract and to investigate the possible influence of diabetes on the zinc and iron content of the lens. Iron and zinc of 57 human lenses (28 corticonuclear cataracts and 29 mature cataracts with a mean age of 70.6 +/- 16.1 and 74.7 +/- 11.1 yr, 41 nondiabetics and 16 diabetics) were determined by atomic absorption spectroscopy. The zinc content of human lenses was significantly increased in mature cataracts compared to corticonuclear cataracts (0.51 +/- 0.33 vs 0.32 +/- 0.20 micromol/g dry mass, p=0.012). The iron content of mature cataracts was also higher than in corticonuclear cataracts (0.11 +/- 0.09 vs 0.07 +/- 0.05 micromol/g dry mass, p=0.071). Furthermore, a significant increase of the lens zinc content could be observed with increasing lens coloration (light brown 0.33 +/- 0.17 vs dark brown 0.52 +/- 0.35 micromol/g dry mass, p=0.032). Diabetic patients seem to have both increased zinc and iron contents in the lens compared to nondiabetic subjects (zinc: 0.45 +/- 0.42 vs 0.40 +/- 0.22 micromol/g dry mass; iron: 0.12 +/- 0.10 vs 0.08 +/- 0.05 micromol/g dry mass). These data suggest a possible influence of the lens zinc and iron content on the development of lens opacification. Especially advanced forms of cataract and dark brown colored lenses show significantly increased zinc and iron content.
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PMID:Increased content of zinc and iron in human cataractous lenses. 1266 21

Hereditary hyperferritinaemia cataract syndrome is an autosomal dominant disorder caused by heterogeneous mutations of the iron regulatory element (IRE) in the ferritin l-chain mRNA. The mutations are rare and fast DNA scanning would facilitate diagnosis. The aim of the study was to compare the analytical performances of two fast DNA scanning techniques: denaturing high-performance liquid chromatography (DHPLC) and double-gradient denaturing gradient gel electrophoresis (DG-DGGE). We analysed the sequence encoding the 5' untranslated flanking region of ferritin l-chain mRNA, which includes an IRE stem loop structure. The two systems unambiguously identified all the 12 accessible mutations in a single run, including the difficult C-G transversions. DHPLC and DG-DGGE identified seven abnormal patterns in DNA samples from 47 subjects with unexplained hyperferritinaemia; all had mutations in the IRE sequence, including two not reported before: C36G and A37G. The scanning of 250 DNA samples from subjects genotyped for HFE led to the identification of four new mutations, all outside the IRE structure: C10T, C16T, C90T and del-T156. We conclude that DHPLC, similar to DG-DGGE, detects all the mutations in the l-ferritin 5'UTR sequence in a single run, and that various mutations occur outside the IRE structure.
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PMID:Scanning mutations of the 5'UTR regulatory sequence of L-ferritin by denaturing high-performance liquid chromatography: identification of new mutations. 1267 Mar 50

Unexplained hyperferritinemia is a common clinical finding, even in asymptomatic persons. When early onset bilateral cataracts are also present, the hereditary hyperferritinemia-cataract syndrome (HHCS), because of heterozygous point mutation in the L ferritin iron-responsive element (IRE) sequence, can be suspected. We sequenced the L ferritin exon 1 in 52 DNA samples from patients referred to us for molecular diagnosis of HHCS. We identified 24 samples with a point mutation/deletion in the IRE. For the 28 samples in which no IRE mutation was present, we also genotyped HFE mutations and sequenced both H ferritin and ferroportin genes. We found an increased frequency of His63Asp heterozygotes (12 of 28) but no H ferritin mutations. We identified 3 new ferroportin mutations, producing, respectively, Asp157Gly, Gln182His, and Gly323Val amino acid replacements, suggesting that these patients have dominant type 4 hemochromatosis. This study demonstrates that both L ferritin IRE and ferroportin mutations can account for isolated hyperferritinemia. The presence of cataract does not permit the unambiguous identification of patients with HHCS, although the existence of a family history of cataract was only encountered in these patients. This raises the intriguing possibility that lens ferritin accumulation might be a factor contributing to age-related cataract in the general population. Additional causes of isolated hyperferritinemia remain to be identified.
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PMID:Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations. 1273 Jan 14

The development of cataracts in Atlantic salmon, Salmo salar L., was studied in 16 groups of smolts fed diets differing in prooxidant (iron, copper, manganese) and antioxidant (vitamin E, vitamin C, astaxanthin) composition and lipid level for 23 weeks in sea water, using a 2(7-3) reduced factorial design. The seven dietary variables were systematically varied at low (requirement level and 150 g lipid kg(-1)) and high levels (below known toxic levels and 320 g lipid kg(-1)). A mean endpoint cataract incidence of approximately 36% was observed. High dietary levels of vitamin C and astaxanthin reduced cataract frequency, whereas high dietary lipid level, iron and manganese were associated with increased cataract frequencies. Considering the nutritional status of selected organs of the fish, only the status of ascorbic acid correlated negatively to cataract development (P < 0.05). The lens glutathione (GSH) status was not correlated to cataract frequency, nor statistically explained by the dietary variables. However, the study shows that balancing the diet with respect to pro- and antioxidant nutrients may significantly protect Atlantic salmon against development of cataracts. An incidence of reversible osmotic cataract observed at week 14 was positively correlated to plasma glucose concentration.
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PMID:Cataract formation in Atlantic salmon, Salmo salar L., smolt relative to dietary pro- and antioxidants and lipid level. 1296 30


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