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)

Conjunctival biopsies from patients with cicatricial pemphigoid affecting the conjunctiva and patients undergoing cataract surgery (normal conjunctiva) were snap-frozen, cryostat sectioned and incubated with fluorescein-conjugated lectins; peanut agglutinin (PNA), Helix pomatia agglutinin (HPA), soybean agglutinin (SBA), wheat germ agglutinin (WGA) and succinylated wheat germ agglutinin (S-WGA). Controls consisted of preincubating the lectins with the appropriate blocking sugars before applying the lectins to the sections. PNA and HPA stained the mucus granules contained in the conjunctival goblet cells but did not stain mucus or glycocalyx at the ocular surface distal to the goblet cells. Native WGA and S-WGA had high affinities for conjunctival goblet cells and the apical epithelial cell layers. Native WGA stained mucus and glycocalyx at the ocular surface. This staining of the ocular surface by WGA was confirmed at the transmission electron microscopic level using WGA conjugated to ferritin. Cicatricial pemphigoid patients in this study had reduced numbers of goblet cells; however, those goblet cells which were observed in cicatricial pemphigoid conjunctiva stained positively with HPA, PNA, WGA, and SWGA as did goblet cells in normal conjunctiva.
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PMID:Detection of ocular mucus in normal human conjunctiva and conjunctiva from patients with cicatricial pemphigoid using lectin probes and histochemical techniques. 328 55

Two human eyes that had undergone intracapsular cataract extraction were perfused with cationized ferritin. In both eyes segmental areas of trabecular meshwork collapse were demonstrated superiorly, adjacent to the cataract incision. Electron-microscopic study of these regions disclosed no labeling of the trabecular beams and trabecular spaces, suggesting impermeability to aqueous flow. In other regions, a diffuse labeling with cationized ferritin was demonstrated throughout the trabecular spaces, indicating aqueous flowthrough. Use of corneoscleral sutures may cause trabecular collapse and impermeability. When the collapse is extensive, subsequent increase in intraocular pressure may follow.
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PMID:Alteration of trabecular aqueous flow after cataract extraction. 344 98

Recently, we described a new genetic disorder (the "hereditary hyperferritinemia-cataract syndrome") clinically characterized by the combination of elevated serum ferritin and congenital bilateral nuclear cataract, both cotransmitted as an autosomal dominant trait. In affected subjects, hyperferritinemia (ranging from 950 to 2,259 micrograms/L) is typically not related to iron overload. Differently from subjects with hereditary hemochromatosis, they have normal to low levels of serum iron and percent of transferrin saturation and absence of iron overload in parenchymal organs. When unnecessary phlebotomies are performed, they rapidly develop iron-deficient anemia, with persistently elevated levels of serum ferritin. By RNA-single-strand conformation polymorphism screening of the L-subunit ferritin gene on chromosome 19, we were able to identify in affected subjects a mutation in the 5' untranslated region. This mutation involves the five nucleotides sequence [CAGUG] of the iron-responsive element (IRE), which is critical for the posttranscriptional regulation of ferritin synthesis by means of IRE-binding protein (IRE-BP). Thus, it is very likely to provide the molecular basis for the iron-insensitive upregulation of ferritin synthesis in affected subjects.
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PMID:Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene (the "Verona mutation") 878 50

The synthesis of ferritin, the iron-storing molecule, is regulated at the translational level by iron through interaction between a cytoplasmic protein, iron regulatory protein (IRP), and a conserved nucleotide motif present in the 5' non-coding region of all ferritin mRNAs--the iron responsive element (IRE). This region forms a stem-loop structure and when the supply of iron to the cells is limited, the IRP is bound to IRE and represses ferritin synthesis. Ferritin is composed of a 24-subunit protein shell surrounding an iron core. The two types of subunit, H and L, are encoded by two genes located on chromosomes 11q13 and 19q13.1, respectively. Both genes are ubiquitously expressed but transcriptional regulation mediates tissue-specific changes in the H/L mRNA ratio and isoferritin profiles. We now report the identification of a single point mutation in the IRE of the L-ferritin mRNA in members from a family affected with dominantly inherited hyperferritinaemia and cataract. This mutation consists of an A to G change in the highly conserved CAGUGU motif that constitutes the IRE loop and mediates the high-affinity interaction with the IRP. We show that this mutation abolishes the binding of IRP in vitro and leads to a high constitutive, poorly regulated L-ferritin synthesis in cultured lymphoblastoid cells established from affected patients. This is, to our knowledge, the first mutation affecting the IRP-IRE interaction and the iron-mediated regulation of ferritin synthesis. We suggest that excess production of ferritin in tissues is responsible for the hyperferritinaemia and that intracellular accumulation of ferritin leads to cataract.
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PMID:Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. 749 28

The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA-related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron-deficiency anaemia. This genetic disorder, which is characterized by hyperferritinaemia, differs from hereditary HLA-related haemochromatosis mostly for the absence of iron overload. A gene responsible for the congenital nuclear cataract likely maps on chromosome 19q close to the ferritin L-subunit gene. Within families with autosomal dominant congenital cataract, serum ferritin might be an early marker of disease.
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PMID:A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract. 766 75

An 81-year-old man with a history of chronic pulmonary disease due to heavy smoking and ischemic heart disease had been suffering for the past few years from chronic constipation and urinary incontinence and was receiving medication for cardiopulmonary symptoms and urinary incontinence. He was admitted for repeated falling for a few months prior to admission. When put in the supine position, his blood pressure fell. He had bilateral pulmonary rales, consistent with lung disease, eccentricity of the left pupil (after cataract surgery), constriction of the right pupil, and absence of the pupillary light reflex. There was generalized hyperreflexia and a bilateral Babinski sign. He had normocytic, normochromic anemia; B12, folic acid and ferritin were within normal ranges, ESR was rapid, there was hyperglobulinemia (IgA and IgG), urea nitrogen and creatinine were increased but returned to normal after rehydration. ECG and chest X-ray were consistent with his cardiopulmonary status. Bone-marrow biopsy showed hypocellularity. IVP and barium enema were normal. Echocardiography revealed a possible old posterior wall myocardial infarction. CT-scan showed moderate cerebral and cerebellar atrophy, calcifications in the carotid and vertebral arteries, and small infarcts in both hemispheres. At this point, after an extensive survey of the literature, the diagnosis of Shy-Drager syndrome was proposed and proved by monitoring ECG and serum levels of noradrenaline during postural changes. He was treated with Fluorinef and there were no more episodes of postural hypotension. Several weeks after discharge he reported that he was feeling well and had not fallen since discharge.
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PMID:[Shy-Drager syndrome]. 775 2

Recent reports have described families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. We have studied the molecular pathogenesis of hyperferritinemia in two families showing different phenotypic expression of this new genetic disorder. Serum ferritin levels ranged from 950 to 1,890 microg/L in affected individuals from family 1, and from 366 to 635 microg/L in those from family 2. Cataract was clinically manifested in family 1 and asymptomatic in family 2. By using monoclonal antibodies specific for the H and L ferritin subunits, serum ferritin was found to be essentially L type in both normal and affected individuals. The latter also showed normal amounts of H-type ferritin in circulating mononuclear cells; on the contrary, L-type ferritin contents were 13 times normal in family 1 and five times normal in family 2 on average. Serum ferritin was glycosylated in both normal and affected individuals. There was a close relationship between mononuclear cell L-type ferritin content and serum ferritin concentration (r = 0.95, P < .00001), suggesting that the excess production of ferritin in cells was directly responsible for the hyperferritinemia. The dysregulated L-subunit synthesis was found to result from different point mutations in a noncoding sequence of genomic L-subunit DNA, which behaves as an mRNA cis-acting element known as iron regulatory element (IRE). Affected individuals from family 1 were heterozygous for a point mutation (a single G to A change) in the highly conserved, three-nucleotide motif forming the IRE bulge. Affected members from family 2 were heterozygous for a double point mutation in the IRE lower stem. Using a gel retardation assay, the observed molecular lesions were shown to variably reduce the IRE affinity for an iron regulatory protein (IRP), which inhibits ferritin mRNA translation. The direct relationship between the degree of hyperferritinemia and severity of cataract suggests that this latter is the consequence of excessive ferritin production within the lens fibers. These findings provide strong evidence that serum ferritin is a byproduct of intracellular ferritin synthesis and that the L-subunit gene on chromosome 19 is the source of glycosylated serum ferritin. From a practical standpoint, this new genetic disorder should be taken into account by clinicians when facing a high serum ferritin in an apparently healthy person.
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PMID:Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA. 1038 91

Iron availability regulates ferritin synthesis posttranscriptionally by the interaction between iron-regulatory proteins (IRPs) and an iron responsive element (IRE), a stem-loop sequence located on the 5' untranslated region of ferritin mRNA. IRPs recognize IREs as a sequence/structure motif, blocking ferritin translation. Recently, we and others independently described families with a combination of hyperferritinemia (serum L-ferritin > or = 1,000 microg/L, without iron overload) and congenital bilateral cataract, transmitted as an autosomal-dominant trait. The molecular basis were two distinct point mutations in the highly conserved CAGUG(X) hexaloop of L-ferritin IRE on chromosome 19. A new three-generation family with a similar phenotype and a unique genotype is here reported. DNA amplification by polymerase chain reaction and sequence analysis showed a 29-base pair deletion in the L-ferritin IRE, involving the whole 5' sequence essential to the base pairing of the IRE stem. This deletion is predicted to cause the disruption of IRE stem-loop secondary structure and the nearly complete abolition of the negative control of ferritin synthesis by IRE/IRP binding. Hereditary Hyperferritinemia-Cataract Syndrome (HHCS) appears as a new genetic disorder with a unique phenotype associated with at least four different mutations in the L-ferritin IRE. Hematologists should take into account HHCS in the differential diagnosis of unexplained hyperferritinemia.
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PMID:Hereditary hyperferritinemia-cataract syndrome caused by a 29-base pair deletion in the iron responsive element of ferritin L-subunit gene. 929 47

The molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome is the presence of a mutation in the iron-responsive element (IRE) of the L ferritin gene, located on chromosome 19q13.3-13.4. Two mutations have been reported so far, altering adjacent nucleotides in the IRE loop, in a region that has been extensively studied in vitro and shown to mediate high affinity interaction with the iron-responsive protein. In this report, we describe two families with a new mutation in the bulge of the IRE stem, and we show that this mutation alters the protein-binding affinity of the IRE in vitro to the same extent as the loop mutation. In addition, we present evidence that some variability in the age of onset of cataract can be associated with this genetic syndrome, probably because of additional genetic or environmental factors that modulate the penetrance of the L ferritin defect in the lens. We confirm that the patients do not have increased iron stores despite the persistence of elevated serum ferritin levels and that, accordingly, they do not tolerate well venesection therapy. Further studies will be necessary to elucidate the mechanism responsible for the onset of cataract.
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PMID:A point mutation in the bulge of the iron-responsive element of the L ferritin gene in two families with the hereditary hyperferritinemia-cataract syndrome. 1038 91

A new autosomal-dominant genetic disorder, which has been recently identified by our group is described. The disease is clinically characterized by the combination of a substantial increase of serum ferritin and early-onset bilateral cataract. Moreover, it is clearly distinguishable from genetic hemochromatosis because of: 1) normal to low serum iron and transferrin saturation, without evidence of parenchymal iron overload; 2) the dominant transmission; 3) the lack of any relation with HLA; 4) the rapid development of iron-deficient anemia when unnecessary phlebotomies are performed. The molecular basis of the new syndrome is a mutation in the L-subunit ferritin gene on chromosome 19 (19q13.3-->19qter). The mutation involves a five nucleotide sequence [CAGUG] of the iron-responsive-element (IRE), which is critical for the post-transcriptional regulation of ferritin synthesis by means of the binding with an Iron Regulatory Protein. As a consequence, ferritin synthesis is up-regulated, irrespective of cell iron status.
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PMID:["Hyperferritinemia-cataract syndrome." Description of a new hereditary disease, from anamnesis to molecular diagnosis]. 941 35


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