Autosomal dominant reticulo-endothelial iron overload associated with a three base pair deletion in the ferroportin 1 gene

Devalia, Vinod; Carter, K.; Walker, A.P.; Perkins, Sara; Worwood, Mark; May, Alison; Dooley, JS

doi:10.1016/s0168-8278(02)80643-2

Cited by 6 publications

(17 citation statements)

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“…Consistent with a pure disorder of iron release (Table 3) some patients have low transferrin saturation, iron-deficient erythropoiesis, and even mild anemia or impaired tolerance of phlebotomy. 79,80 These patients do not develop iron-related clinical complications. However, patients who carry other mutations accumulate iron in hepatocytes and develop clinical signs of iron-induced damage, as in classic hemochromatosis.…”

Section: Ferroportin Disease: a Hemochromatosis-related Dual Face Dismentioning

confidence: 89%

“…78 A recurrent deletion (162del-Val) has been reported in unrelated families. 79,80 A SLC40A1 mutation has also been characterized in a single patient from Solomon Islands. 81 A disease caused by heterozygous mutations in the iron exporter ferroportin generated a controversy as to whether these mutations might cause a gain or a loss of the metal exporter function.…”

Section: Ferroportin Disease: a Hemochromatosis-related Dual Face Dismentioning

confidence: 99%

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Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders

Camaschella

2005

Blood

184

130

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Genetic analysis of hemochromatosis has led to the discovery of a number of genes whose mutations disrupt iron homeostasis and lead to iron overload. The introduction of molecular tests into clinical practice has provided a tool for early diagnosis of these conditions. It has become clear that hemochromatosis includes a spectrum of disorders that range from simple biochemical abnormalities to chronic asymptomatic tissue damage in midlife to serious life-threatening diseases in young subjects. Molecular studies have identified the systemic loop that controls iron homeostasis and is centered on the hepcidin-ferroportin interaction. The complexity of this regulatory pathway accounts for the genetic heterogeneity of hemochromatosis and related disorders and raises the possibility that genes encoding components of the pathway may be modifiers of the main genotype. Molecular diagnosis has improved the classification of the genetic conditions leading to iron overload and identified novel entities, characterized by both iron loading and variable degrees of anemia. Despite the progress in the diagnosis, classification, and mechanisms of iron overload disorders, the treatment of affected patients continues to rely on regular phlebotomy. Understanding the molecular circuitry of iron control may lead to the identification of potential therapeutic targets for novel treatment strategies to be used in association with or as an alternative to phlebotomy. (Blood. 2005;106:3710-3717)

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Section: Ferroportin Disease: a Hemochromatosis-related Dual Face Dismentioning

confidence: 89%

Section: Ferroportin Disease: a Hemochromatosis-related Dual Face Dismentioning

confidence: 99%

Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders

Camaschella

2005

Blood

184

130

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“…This protein is expressed mainly in enterocytes and macrophages, but the presence of Ireg1 also has been described in neurons, glioma cells and astrocytes (5,13,22). In enterocytes, Ireg1 is responsible for iron efflux during the process of intestinal iron absorption, while in Kupffer cells Ireg1 mediates iron export for reutilization by the bone marrow (11). The mechanism underlying regulation of Ireg1 expression is unknown, but it is clearly cell-specific; in enterocytes, iron deficiency induces Ireg1 expression (27), whereas in macrophages iron deficiency decreases Ireg1 expression (7).…”

Section: Iron Accumulation: Roles Of the Iron Transporters Dmt1 And Imentioning

confidence: 99%

Iron and glutathione at the crossroad of redox metabolism in neurons

et al. 2006

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Neurons, as non-dividing cells, encounter a myriad of stressful conditions throughout their lifespan. In particular, there is increasing evidence that iron progressively accumulates in the brain with age and that ironinduced oxidative stress is the cause of several forms of neurodegeneration. Here, we review recent evidence that gives support to the following notions: 1) neuronal iron accumulation leads to oxidative stress and cell death; 2) neuronal survival to iron accumulation associates with decreased expression of the iron import transporter DMT1 and increased expression of the efflux transporter IREG1; and 3) the adaptive process of neurons towards iron-induced oxidative stress includes a marked increase in both the expression of the catalytic subunit of gamma glutamate-cysteine ligase and glutathione. These findings may help to understand aging-related neurodegeneration hallmarks: oxidative damage, functional impairment and cell death.

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“…Ferroportin 1 gene mutation is clearly associated with the development of an iron overload phenotype predominant in macrophages, suggesting a role of this protein in cellular iron egress [16][17][18][19][20][21][22]. In patients with genetic haemochromatosis related to C282Y HFE gene mutations (HFE-1 haemochromatosis), despite strong iron overload, no iron accumulates within reticulo-endothelial cells, including those located in spleen, conversely to secondary iron overload [23].…”

Section: Control Of Iron Release From Macrophagesmentioning

confidence: 99%

Hepcidin in Iron Metabolism

Loréal¹,

Haziza-Pigeon²,

Troadec³

et al. 2005

CPPS

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Hepcidin, which has been recently identified both by biochemical and genomic approaches, is a 25 amino acid polypeptide synthesized mainly by hepatocytes and secreted into the plasma. Besides its potential activity in antimicrobial defense, hepcidin plays a major role in iron metabolism. It controls two key steps of iron bioavailability, likely through a hormonal action: digestive iron absorption by enterocytes and iron recycling by macrophages. In humans, this could explain that low levels of hepcidin found during juvenile haemochromatosis and HFE-1 genetic haemochromatosis are associated with an iron overload phenotype. Conversely, an increase of hepcidin expression is suspected to play a major role in the development of anemia of chronic inflammatory diseases. However, the regulatory mechanisms of hepcidin expression are multiple, including iron-related parameters, anemia, hypoxia, inflammation and hepatocyte function. Therefore, many physiological and pathological situations may modulate hepcidin expression and subsequently iron metabolism. A better knowledge of the biological effects of hepcidin and of its expression regulatory mechanisms will clarify the place of hepcidin in the diagnosis and treatment of iron-related diseases.

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Autosomal dominant reticulo-endothelial iron overload associated with a three base pair deletion in the ferroportin 1 gene

Cited by 6 publications

References 0 publications

Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders

Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders

Iron and glutathione at the crossroad of redox metabolism in neurons

Hepcidin in Iron Metabolism

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