A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload

Kannengiesser, Caroline; Jouanolle, Anne–Marie; Hetet, Gilles; Mosser, Annick; Muzeau, Françoise; Henry, Dominique; Bardou-Jacquet, Édouard; Mornet, M; Brissot, Pierre; Deugnier, Yves; Grandchamp, Bernard; Beaumont, Carole

doi:10.3324/haematol.2008.000125

Cited by 76 publications

(61 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 There are also missense mutations in the coding region of FTL (p.Thr30Ile, p. Gln26Ile and p.Ala27Val) known to cause hyperferritinaemia associated with hyperglycosylation of ferritin, without iron overload or cataracts. 7,8 HHCS normally follows an autosomal dominant pattern of inheritance. Cases of de novo mutation are also known, which have been referred to as 'nonhereditary hyperferritinemia cataract syndrome' by Cao et al 9 or more simply 'hyperferritinaemia cataract syndrome'.…”

Section: Discussionmentioning

confidence: 99%

A novel deletion in the iron-response element of the L-ferritin gene, causing hyperferritinaemia cataract syndrome

Garber

Pudek

2014

Ann Clin Biochem

View full text Add to dashboard Cite

A 47-year-old woman, presenting to her family physician with fatigue, was incidentally found to have persistently elevated ferritin. There was clinically no suggestion of iron overload, and laboratory testing showed transferrin saturation at the low end of the reference range. After ruling out acquired causes of hyperferritinaemia, as well as laboratory interference, further questioning revealed a history of bilateral early-onset cataracts, allowing a diagnosis of hyperferritinaemia cataract syndrome to be made. DNA sequencing of the 5 0 untranslated region of the L-ferritin gene revealed a novel 4-base deletion in the iron response element, within a region known to be crucial for binding iron regulatory protein.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel deletion in the iron-response element of the L-ferritin gene, causing hyperferritinaemia cataract syndrome

Garber

Pudek

2014

Ann Clin Biochem

View full text Add to dashboard Cite

show abstract

“…Numerous type of mutations have been identified; they all reduce the affinity of the IRE for IRPs, thus resulting in a constitutive overexpression of the FtL protein. This seems to cause ferritin L precipitation in the lenses (Goralska et al 2001;Kannengiesser et al 2009), but no alterations of iron homeostasis, even though the FtL excess occurs in all tissues. Also FtL haploinsufficiency did not lead to any clinical manifestation or evident perturbation of iron homeostasis (Cremonesi et al 2004) and one case with homozygous inactivation of FtL gene did not show evident problems in iron regulation but some neurological defects, such as idiopathic generalized seizures and atypical restless leg syndrome (Cozzi et al 2013).…”

Section: Ferritin Mutations In Genetic Disordersmentioning

confidence: 99%

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

2014

View full text Add to dashboard Cite

Iron is an abundant transition metal that is essential for life, being associated to many enzyme and oxygen carrier proteins involved in a variety of fundamental cellular processes. At the same time the metal is potentially toxic due to its capacity to engage in the catalytic production of noxious reactive oxygen species. The control of iron availability in the cells is largely dependent on ferritins, ubiquitous proteins with storage and detoxification capacity. In mammals, cytosolic ferritins are composed of two types of subunits, the H and the L chain, assembled to form a 24-mer spherical cage. Ferritin is present also in mitochondria, in the form of a complex with 24 identical chains. Even though the proteins have been known for a long time, their study is a very active and interesting field yet. In this review we will focus our attention to mammalian cytosolic and mitochondrial ferritins, describing the most recent advancement regarding their storage and antioxidant function, the effects of their genetic mutations in human pathology, and also the possible involvement in non-iron related activities. We will also discuss recent evidence connecting ferritins and the toxicity of iron in a set of neurodegenerative disorder characterized by focal cerebral siderosis. IntroductionThe adaptation of life to an oxic environment required the development of mechanisms to deal with the transformation of the water soluble ferrous ion (Fe 2+ ) to the insoluble ferric ion (Fe 3+ ) and with the concomitant generation of dangerous reactive oxygen species (ROS). The ferritin molecules represent an important and ancient mean developed by organisms in the three domains of life to safely handle the necessary, yet potentially toxic metal. Their ability to detoxify and store the metal through safe oxidation processes protects the cells from undue iron-dependent redox chemistry, while a controlled release of the metal guarantees its availability for different and essential enzymatic reactions. Storage and detoxification of iron represent the main functions of these molecules, and much work has been done to understand the chemical and molecular details of this

show abstract

“…Except for eye surgery, no treatment is required: the few patients who have been treated with phlebotomy developed anemia without changes in serum ferritin levels. 15 In this issue of the journal, Kannengiesser et al 18 report a novel genetic dominant hyperferritinemia, that appears to have a benign course in the absence of iron overload (indicated as benign hyperferritinemia in Table 1 and Figure 1). These authors have collected a large number of samples from both familial (n=25) and isolated (n=66) subjects with unexplained hyperferritinemia.…”

confidence: 99%

Towards explaining "unexplained hyperferritinemia"

Camaschella¹,

Poggiali²

2009

Haematologica

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o nIron (NTBI), the toxic moiety of iron, responsible for liver damage and eventually damage to the heart, pancreas and pituitary gland. Very high levels of ferritin may be found in hemochromatosis type 4 or ferroportin disease which does not result from impaired hepcidin but rather from heterozygous mutations of the hepcidin receptor ferroportin. 5 The disease is autosomal dominant and has a variable clinical phenotype. The true ferroportin disease (hemochromatosis type 4a in Table 1) is due to mutant proteins that are not correctly targeted to the cell surface and is characterized by macrophage iron accumulation, low/normal transferrin saturation and iron-restricted erythropoiesis.6 A second form (hemochromatosis type 4b), due to mutant ferroportins that reach the cell surface but are resistant to hepcidin-induced internalization, 7 is characterized by hepatocyte iron accumulation and high transferrin saturation, as in hemochromatosis. The distinction is clinically relevant, because the true ferroportin disease seems not to be associated with clinical complications. These observations strengthen the relevance of assessing serum ferritin always in the context of transferrin saturation ( Figure 1).Ferritin is increased in iron overload secondary to chronic blood transfusions irrespective of the reason and also in the so called iron loading anemias, which include beta-thalassemia syndromes 8 and congenital sideroblastic or dyserythropoietic anemias, 9 characterized by high levels of ineffective erythropoiesis and low hepcidin production. All these conditions are usually well known from the patient's history and may be diagnosed by specific tests. Several methods such as magnetic resonance imaging (MRI) 10 or SQUID 11 have become available to non-invasively assess hepatic iron concentration: however, serial ferritin determinations remain a useful guide to assess iron overload and to monitor iron chelation therapy in these patients. 12Moderate increase of serum ferritin with normal/high transferrin saturation and mild/moderate liver iron accumulation may be common in chronic liver disorders, such as alcoholic liver disease and chronic viral hepatitis. These conditions require attention because iron may amplify the toxic effect of alcohol and viruses, accelerating the evolution towards fibrosis and cirrhosis. In porphyria cutanea tarda hyperferritinemia is a sign of iron overload (in some cases due to HFE mutations) 13 and, like alcohol and chronic hepatitis, is a trigger of porphyria attacks.In the metabolic syndrome (variable combination of hypertension, diabetes, hypertrigliceridemia, obesity, steatohepatitis or fatty liver) moderate elevation of ferritin is common, but usually ferritin levels are disproportionately high in comparison with iron stores, 14 whereas transferrin saturation is not increased.In recent years, new forms of inherited hyperferritinemia not associated with iron overload have been identified, adding new elements for differential diagnosis. A rare d...

show abstract

A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload

Cited by 76 publications

References 22 publications

A novel deletion in the iron-response element of the L-ferritin gene, causing hyperferritinaemia cataract syndrome

A novel deletion in the iron-response element of the L-ferritin gene, causing hyperferritinaemia cataract syndrome

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

Towards explaining "unexplained hyperferritinemia"

Contact Info

Product

Resources

About