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)

We examined 63 patients with beta-thalassemia whose ages range from 7 to 57 years. Lens opacities were presented in 14 patients--22%. The period these persons had transfusions and were submitted to iron chelating drug--deferoxamine and the concentration of there serum ferritin in the last seven years were noted. Comparing persons with identical ages and transfusion periods we found that patients who were submitted to less chelation therapy patients which started these therapy later and patients with higher values of mean ferritin or with significant picks were in danger to developed cataract. Patients younger of 10 years old didn't developed cataract despite high values of ferritin. All patients after 30 did have lens opacities.
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PMID:[The mechanism of cataract formation in persons with beta-thalassemia]. 1041 22

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a novel genetic disorder characterized by elevated serum ferritin and early onset cataract formation. The excessive ferritin production in HHCS patients arises from aberrant regulation of L-ferritin translation caused by mutations within the iron-responsive element (IRE) of the L-ferritin transcript. IREs serve as binding sites for iron regulatory proteins (IRPs), iron-sensing proteins that regulate ferritin translation. Previous observations suggested that each unique HHCS mutation conferred a characteristic degree of hyperferritinemia and cataract severity in affected individuals. Here we have measured the in vitro affinity of the IRPs for the mutant IREs and correlated decreases in binding affinity with clinical severity. Thermodynamic analysis of these IREs has also revealed that although some HHCS mutations lead to changes in the stability and secondary structure of the IRE, others appear to disrupt IRP-IRE recognition with minimal effect on IRE stability. HHCS is a noteworthy example of a human genetic disorder that arises from mutations within a protein-binding site of an mRNA cis-acting element. Analysis of the effects of these mutations on the energetics of the RNA-protein interaction explains the phenotypic variabilities of the disease state.
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PMID:Clinical severity and thermodynamic effects of iron-responsive element mutations in hereditary hyperferritinemia-cataract syndrome. 1047 3

Tight regulation of iron metabolism is crucial to avoid formation of deleterious radicals and is mainly executed at the post-transcriptional level. The regulatory loops are exerted by trans-acting iron regulatory proteins (IRPs) and cis-acting stem-loop motifs, termed iron-responsive elements (IREs), located in the untranslated regions (UTRs) of target mRNAs. Iron scarcity induces binding of IRPs to a single IRE in the 5'-UTR of ferritin, eALAS, aconitase and SDHb mRNAs, which specifically suppresses translation initiation. Simultaneous interaction of IRPs with multiple IREs in the 3'-UTR of transferrin receptor (TfR) mRNA selectively causes its stabilization. The pattern is reverted under iron overload: IRP-mRNA binding affinity is reduced, which results in efficient protein synthesis of target transcripts harboring IREs in the 5'-UTR and rapid degradation of TfR mRNA. Although multiple evidences support this model, several studies reported massive alterations in the regulation of iron homeostasis under specific physiological conditions, raising the possibility for additional regulatory events. Intensive analysis of the palindromic IRE consensus sequence revealed the critical elements for the formation of a functional structure and demonstrated the consequences of IRE mutations in IRP binding. Recent investigations indicated the involvement of naturally occurring IRE mutations of the ferritin L subunit in the hyperferritinemia-cataract syndrome, a hereditary disorder. This review summarizes the apparent links between iron-dependent post-transcriptional control and its abnormalities, governed by the properties of a single mRNA stem-loop structure.
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PMID:Post-transcriptional control via iron-responsive elements: the impact of aberrations in hereditary disease. 1059 29

Recent research in iron metabolism has revealed the existence of iron-responding elements in the 5'UTR of the mRNA of ferritin. Binding of these structures with iron-regulatory proteins regulates ferritin synthesis within the cell, according to the intracellular iron level. Several mutations of the iron-responding elements located at the 5'UTR of the L-ferritin subunit, which lead to the hereditary hyperferritinaemia cataract syndrome, an autosomal dominant hereditary disease, have been described. Patients with congenital bilateral nuclear cataract present high serum ferritin (360-2264 micrograms/l) in the absence of iron overload. The purpose of our study was to look for this syndrome in Switzerland and in particular in the Geneva population. About 3000 cases of cataract operated on during a 4-year period (1995-1998) in the University Clinic of Ophthalmology were screened. We found 135 patients operated on before the age of 51 years. However, only 19 had bilateral nuclear cataract. 15 patients agreed to undergo iron screening. In 2 of them, a slight elevation of ferritin (267 micrograms/l in a female, 416 micrograms/l in a male) was found in the absence of iron overload. In both cases there is a positive family history of cataract. DNA sequencing analysis in these patients showed a normal nucleotide sequence of the whole iron-responding elements region. One of them (male) was found to present the codon 63 mutation at HFE gene in the heterozygous state. Our local study indicates that hereditary hyperferritinaemia cataract syndrome is extremely rare in Switzerland. However, similar studies should be carried out in other regions of the country. Iron status evaluation and ferritin level monitoring should become routine examinations in all new cases presenting with bilateral nuclear cataract before the age of 50 years.
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PMID:Hereditary hyperferritinaemia cataract syndrome: does it exist in Switzerland? 1074 72

The iron content of the body is normally closely regulated. Despite this, iron deficiency anaemia is common in women because iron losses due to menstruation and childbirth are not always compensated for by iron absorption from the diet. The role of transferrin in delivering iron to cells and of ferritin in storing iron within cells is well understood but the proteins involved in iron transport across membranes are only now being investigated. Relatively few genetic disorders affecting iron metabolism are known and most are rare. This paper briefly describes pyridoxine responsive sideroblastic anaemia, hyperferritinaemia-cataract syndrome, atransferrinaemia and genetic haemochromatosis. Rather than rare, the latter is one of the most common inherited disorders in northern European populations. Mutations in genes regulating membrane iron transport causing simple iron deficiency have not yet been described.
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PMID:Inborn errors of metabolism: iron. 1074 46

Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.
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PMID:A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins. 1075 2

Remarkable progress is being made in understanding the molecular basis of disorders of human iron metabolism. Recent work has uncovered unanticipated relationships with the immune and nervous systems, intricate interconnections with copper metabolism, and striking homologies between yeast and human genes involved in the transport of transition metals. This review examines the clinical consequences of new insights into the pathophysiology of genetic abnormalities affecting iron metabolism. The proteins recently found to be involved in the absorption, transport, utilization, and storage of iron are briefly described, and the clinical manifestations of genetic disorders that affect these proteins are discussed. This chapter considers the most common inherited disorder in individuals of European ancestry (hereditary hemochromatosis), a widespread disease in sub-Saharan populations for which the genetic basis is still uncertain (African dietary iron overload), and several less frequent or rare disorders (juvenile hemochromatosis, atransferrinemia, aceruloplasminemia, hyperferritinemia with autosomal dominant congenital cataract, Friedreich's ataxia, and X-linked sideroblastic anemia with ataxia).
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PMID:Genetic disorders affecting proteins of iron metabolism: clinical implications. 1077 76

Oxidative effects on lens proteins have been linked with the formation of human age-related cataract, particularly nuclear cataract. This study investigated the effects of hyperbaric oxygen (HBO)-induced oxidative stress on nuclear and cortical alpha-, beta- and gamma-crystallins of cultured rabbit lenses, using high performance liquid chromatography (HPLC). The lenses were treated with 50 atm of either 100% N(2)(control) or 100% O(2)(experimental) for 3, 6, 16 and 48 hr. The levels of reduced glutathione (GSH) and water-soluble (WS) protein decreased more rapidly in the nucleus of the O(2)-treated lens than in the cortex. The first significant loss of WS protein in each of the two regions occurred when levels of GSH had decreased by at least 90% in either the nucleus (at 6 hr) or the cortex (at 16 hr). HPLC analysis of the nuclear WS proteins indicated that beta-crystallins were the first proteins affected by the oxidative stress. Soon after HBO-treatment was initiated (at 6 hr) and prior to insolubilization of protein, nuclear beta- and gamma-crystallins moved to the higher molecular weight alpha-crystallin fraction; 2-D gel electrophoresis and Western blotting indicated the presence of disulfide-crosslinked and non-crosslinked beta- and gamma-crystallins in this fraction. Significantly different HBO-induced effects were observed on lens cortical crystallins compared to those for the nucleus. For example, gamma-crystallins in the cortex shifted very soon after HBO-treatment (at 3 hr) to slightly higher molecular weights, possibly the result of protein/glutathione mixed disulfide formation; however, this phenomenon was not observed in the nucleus. Cortical beta- and gamma-crystallins remained in solution longer than nuclear proteins following HBO-treatment of the lenses, presumably the result of protection from the four-fold higher level of GSH (22 vs 6 m M) present in the lens periphery. Surprisingly, there was no movement of beta- and gamma-crystallins to alpha(H)- and alpha-crystallin fractions in the cortex of the O(2)-treated lens, in contrast to that observed for the nucleus. Cortical crystallins appeared to go directly from being soluble to being insoluble with no high molecular weight intermediate stage. The data suggested a possible chaperone-like function for alpha-crystallin in the nucleus of the stressed lenses, but not in the cortex. HBO-induced effects on lens nuclear supernatants, which mimicked those observed for intact lenses, could be nearly completely prevented by the copper-chelator bathocuproine, but not by the iron-chelator deferoxamine. Overall, the results provide additional evidence demonstrating an increased susceptibility of the lens nucleus to oxidative stress; the greater protective ability of the cortex may be linked to a higher capacity for beta- and gamma-crystallin/glutathione mixed disulfide formation, inhibiting disulfide-crosslinked insolubilization. The data also implicate copper as a catalyst for the autoxidation of -SH groups in the lens, and suggest that alpha-crystallin chaperone-like activity may play a greater role in the lens nucleus than in the cortex in preventing oxidative insolubilization of crystallins.
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PMID:The effects of hyperbaric oxygen on the crystallins of cultured rabbit lenses: a possible catalytic role for copper. 1099 58

The case of a male infant who was found to have hyperferritinemia was made at the age of 3 months is described. The patient and several members of his family from three generations were diagnosed with hereditary hyperferritinemia-cataract syndrome with a new point mutation in the iron-responsive element of the L-ferritin gene. Differential diagnosis of hyperferritinemia is discussed with emphasis on the need for the knowledge of this entity to avoid unnecessary investigations.
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PMID:[Isolated hyperferritinemia in a healthy male infant: hereditary hyperferritinemia-cataract syndrome]. 1246 62

A 23-year-old woman had bilateral myopic laser in situ keratomileusis (LASIK). Two months postoperatively, she reported decreased visual acuity. Biomicroscopic examination revealed a corneal epithelial iron ring around the central keratectasia on both corneas. The appearance of the ring pattern was similar to the iron deposits of the Fleischer ring of keratoconus.
J Cataract Refract Surg 2000 Nov
PMID:Corneal iron ring associated with iatrogenic keratectasia after myopic laser in situ keratomileusis. 1149 5


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