A novel mutation in the CUB sequence of matriptase‐2 (<i>TMPRSS6</i>) is implicated in iron‐resistant iron deficiency anaemia (IRIDA)

Jaspers, Aurélie; Caers, Jo; Gac, Gérald Le; Férec, Claude; Béguin, Yves; Fillet, Georges

doi:10.1111/bjh.12147

Cited by 18 publications

(21 citation statements)

References 9 publications

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“…Interestingly, in contrast to current understanding of autosomal recessive disorder, haploinsufficiency is observed in some TMPRSS6 mutations ( Figure 1 ; Finberg et al, 2008; Pellegrino et al, 2012; Jaspers et al, 2013). Haploinsufficiency is also observed in animal models.…”

Section: Tmprss6 Mutations In Mice and Humancontrasting

confidence: 60%

The role of TMPRSS6/matriptase-2 in iron regulation and anemia

2014

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Matriptase-2, encoded by the TMPRSS6 gene, is a member of the type II transmembrane serine protease family. Matriptase-2 has structural and enzymatic similarities to matriptase-1, which has been implicated in cancer progression. Matriptase-2 was later established to be essential in iron homeostasis based on the phenotypes of iron-refractory iron deficiency anemia identified in mouse models as well as in human patients with TMPRSS6 mutations. TMPRSS6 is expressed mainly in the liver and negatively regulates the production of hepcidin, the systemic iron regulatory hormone. This review focuses on the current understanding of matriptase-2 biochemistry, and its role in iron metabolism and cancer progression. In light of recent investigations, the function of matriptase-2 in hepcidin regulation, how it is being regulated, as well as the therapeutic potential of matriptase-2 are also discussed.

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Section: Tmprss6 Mutations In Mice and Humancontrasting

confidence: 60%

The role of TMPRSS6/matriptase-2 in iron regulation and anemia

2014

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“…To date, five other mutations responsible for IRIDA have been identified in the second CUB domain of TMPRSS6 : p.Y355X, p.H369N, p.Y393X, p.Y418C, and p.G442R . Mutagenesis and expression studies of p.Y418C showed that although it was characterized by a reduction in autoactivating cleavage, it retained some of its transcriptional repression activity.…”

Section: Discussionmentioning

confidence: 99%

Novel mutation in the TMPRSS6 gene with iron‐refractory iron deficiency anemia

Kodama

Noguchi

Adachi

et al. 2014

Pediatrics International

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Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal recessive disease characterized by congenital hypochromic microcytic anemia, low transferrin saturation, low serum iron, normal-high serum ferritin, and increased hepcidin. This disease is caused by loss-of-function mutations in TMPRSS6 that lead to high hepcidin and result in severe anemia. We report our experience with an 11-year-old Japanese girl with hypochromic microcytic anemia, low serum iron, and high serum ferritin, with anemia that was refractory to the oral iron that was prescribed frequently from early childhood. Presence of high hepcidin suggested a diagnosis of IRIDA, which was eventually confirmed by identification of a novel homozygous mutation, p.Pro354Leu, in the TMPRSS6 gene. This case suggests that serum hepcidin should be routinely measured for differential diagnosis when patients with IDA are unresponsive to oral iron or have unusual clinical features.

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“…85 Up to the present, over 50 patients from 34 families have been reported with a wide range of ethnic origins representing .40 different TMPRSS6 mutations. 76,86,87 TMPRSS6 polymorphisms have been associated with variation in iron parameters 88 and with increased risk of iron deficiency. 89 Interestingly, TMPRSS6 variants were associated with IDA in a small series of autoimmune gastritis patients with polyendocrine autoimmune syndrome 90 suggesting an interplay between genetic and acquired factors in refractory IDA.…”

Section: Hereditary Iron-refractory Iron Deficiency Syndrome (Irida)mentioning

confidence: 99%

How I treat unexplained refractory iron deficiency anemia

Hershko

Camaschella

2014

Blood

133

140

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Endoscopic gastrointestinal workup fails to establish the cause of iron deficiency anemia (IDA) in a substantial proportion of patients. In patients referred for hematologic evaluation with unexplained or refractory IDA, screening for celiac disease, autoimmune gastritis, Helicobacter pylori, and hereditary forms of IDA is recommended. About 4% to 6% of patients with obscure refractory IDA have celiac disease, and autoimmune gastritis is encountered in 20% to 27% of patients. Stratification by age cohorts in autoimmune gastritis implies a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. Over 50% of patients with unexplained refractory IDA have active H pylori infection and, after excluding all other causes of IDA, 64% to 75% of such patients are permanently cured by H pylori eradication. In young patients with a history suggestive of hereditary iron deficiency with serum ferritin higher than expected for IDA, mutations involving iron trafficking and regulation should be considered. Recognition of the respective roles of H pylori, autoimmune gastritis, celiac disease, and genetic defects in the pathogenesis of iron deficiency should have a strong impact on the current diagnostic workup and management of unexplained, or refractory, IDA.

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A novel mutation in the CUB sequence of matriptase‐2 (TMPRSS6) is implicated in iron‐resistant iron deficiency anaemia (IRIDA)

Cited by 18 publications

References 9 publications

The role of TMPRSS6/matriptase-2 in iron regulation and anemia

The role of TMPRSS6/matriptase-2 in iron regulation and anemia

Novel mutation in the TMPRSS6 gene with iron‐refractory iron deficiency anemia

How I treat unexplained refractory iron deficiency anemia

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