A new mutation (G51C) in the iron‐responsive element (IRE) of <scp>l</scp>‐ferritin associated with hyperferritinaemia–cataract syndrome decreases the binding affinity of the mutated IRE for iron‐regulatory proteins

Camaschella, Clara; Zecchina, Gabriella; Lockitch, Gillian; Roetto, Antonella; Campanella, Alessandro; Arosio, Paolo; Levi, Sonia

doi:10.1046/j.1365-2141.2000.01920.x

Cited by 39 publications

(15 citation statements)

References 14 publications

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“…In contrast, treatment with iron alone (transferrin-bound or nontransferrin-bound iron) induced the synthesis of L ferritin. 82 Overexpression of myotonic dystrophy protein kinase in C2C12 24,193,194,195,196,197,198,199,200,201,202,203 Ferritin L non-IRE mutations Neuroferritinopathy 64…”

Section: Ferritin Regulation By Cytokines and Inflammationmentioning

confidence: 99%

Regulation of ferritin genes and protein

Torti

2002

Blood

986

819

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Section: Ferritin Regulation By Cytokines and Inflammationmentioning

confidence: 99%

Regulation of ferritin genes and protein

Torti

2002

Blood

986

819

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“…It has been shown by several researchers that mutated IREs have a markedly reduced binding affinity for both IRP1 and IRP2. [6][7][8][9] As a result, ferritin synthesis remains elevated, even under conditions of iron depletion. In the first 2 families described, point mutations were identified in 2 different nucleotides coding for the IRE loop, which resulted in a 40AϾG 6 and a 41GϾC 10 change at the heterozygous state (numbering starts at the cap site of the L ferritin mRNA).…”

Section: Introductionmentioning

confidence: 99%

Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations

Hetet

Devaux

Soufir

et al. 2003

Blood

127

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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. (Blood. 2003;102: 1904-1910

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“…Identification of additional HFE mutations or variants in iron-regulating genes [59][60][61][62][63] may eventually justify neonatal screening for early detection and ongoing surveillance of individuals at highest risk for developing iron overload. Systematic studies on the natural history of HHC are first needed to distinguish those individuals with the risk genotype who will most likely benefit from early treatment from those who will remain asymptomatic.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Hfe Mutations in California Newborns

Hoppe

Watson

Long

et al. 2006

Pediatric Hematology and Oncology

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Advances in molecular diagnostics have led to an increased interest in expanding population-based screening to include genetic diseases that occur outside the newborn period. Hereditary hemochromatosis may be a candidate for large-scale screening in populations with a high prevalence of the common HFE mutations. To determine race-specific frequencies of the HFE mutations, C282Y and H63D, the authors applied an automated, high-throughput genotyping method to dried blood spot samples from a representative population of California newborns. In this sample of 3989 newborns, C282Y and H63D allele frequencies were highest in white (C282Y: 5.5 +/- 0.5%; H63D: 13.4 +/- 0.76%) and Hispanic (C282Y: 1.8 +/- 0.29%; H63D: 11.9 +/- 0.72%) newborns, and lowest in black (C282Y: 1.3 +/- 0.25%; H63D: 3.0 +/- 0.38%) and Asian (C282Y 0.5 +/- 0.16%; H63D 2.9 +/- 0.37%) newborns. The estimated prevalence of C282Y homozygotes in this multiracial population is 1.4/1000. As additional genetic and environmental risk factors for HHC are identified, neonatal screening may become an acceptable strategy to follow susceptible individuals and prevent clinical disease.

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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

Cited by 39 publications

References 14 publications

Regulation of ferritin genes and protein

Regulation of ferritin genes and protein

Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations

Prevalence of Hfe Mutations in California Newborns

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