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)

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

The hyperferritinemia-cataract syndrome, inherited as a Mendelian dominant trait, is due to mutations in the 5' non-coding region of the ferritin light chain gene that modifies the shape of the IRE (iron responsive element) region, which loses its normal function of regulating the synthesis of ferritin light chains. Excess of light chains results in complexes that accumulate into the lens giving rise to early cataracts. We present a Spanish family with seven affected members through three generations. A genetic study reveals a substitution of a single base (C-->T) at position 33 in the IRE sequence in the index case and in one affected brother, whereas a non-affected sister shows the normal sequence. The hyperferritinemia-cataract syndrome was identified in 1995 and is still poorly understood. Clinicians should suspect it when treating any subject with early cataracts, even more if they are familial, or in patients with very high levels of ferritinemia without evidence of iron overload. There are no known consequences of the syndrome other than cataracts, and its proper diagnosis carries a favorable prognosis and eliminates the risk of unnecessary phlebotomies.
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PMID:Hereditary hyperferritinemia-cataract syndrome. Study of a new family in Spain. 1528 33

The hereditary hyperferritinaemia-cataract syndrome (HHCS) is characterised by an autosomal dominant cataract and high levels of serum ferritin without iron overload. The cataract develops due to L-ferritin deposits in the lens and its pulverulent aspect is pathognomonic. The syndrome is caused by mutations within the iron-responsive element of L-ferritin. These mutations prevent efficient binding of iron regulatory proteins 1 and 2 to the IRE in L-ferritin mRNA, resulting in an unleashed ferritin translation. This paper reviews all 31 mutations (27 single nucleotide transitions and four deletions) that have been described since 1995. Laboratory test showing hyperferritinaemia, normal serum iron and normal transferrin saturation are indicative for HHCS after exclusion of other causes of increased ferritin levels (inflammation, malignancy, alcoholic liver disease) and should prompt an ophthalmological consultation for diagnostic confirmation. Invasive diagnostics such as liver biopsy are not indicated. HHCS is an important differential diagnosis of hyperferritinaemia. Haematologists, gastroenterologists and ophthalmologists should be aware of this syndrome to spare patients from further invasive diagnosis (liver biopsy), and also from a false diagnosis of hereditary haemochromatosis followed by venesections. Patients diagnosed with HHCS should be counselled regarding the relative harmlessness of this genetic disease, with early cataract surgery as the only clinical consequence.
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PMID:Hyperferritinaemia-cataract syndrome: worldwide mutations and phenotype of an increasingly diagnosed genetic disorder. 2051 Nov 38