A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. (Articolo in rivista) (literal)

Anno

• 2008-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.3324/haematol.13342 (literal)

Alternative label

• Maria Antonietta Melis; Milena Cau; Rita Congiu; Gabriella Sole; Susanna Barella; Antonio Cao; Mark Westerman; Mario Cazzola; Renzo Galanello (2008)
  A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron.
  in Haematologica (Roma)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Maria Antonietta Melis; Milena Cau; Rita Congiu; Gabriella Sole; Susanna Barella; Antonio Cao; Mark Westerman; Mario Cazzola; Renzo Galanello (literal)

Pagina inizio

• 1 (literal)

Pagina fine

• 7 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 93 (literal)

Rivista

• Haematologica (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 7 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 10 (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Melis MA, Cau M, Congiu R, Galanello R: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Italy; Sole G, Cao A : Istituto di Neurogenetica e Neurofarmacologia, CNR, Cagliari; Barella S: Ospedale Regionale Microcitemie, Clinica Pediatrica 2, Cagliari, Italy; Westerman M: Intrinsic LifeSciences, LLC, La Jolla, CA, USA ; Cazzola M: Department of Hematology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (literal)

Titolo

• A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. (literal)

Abstract

• Background Hepcidin plays a key role in body iron metabolism by preventing the release of iron from macrophages and intestinal cells. Defective hepcidin synthesis causes iron loading, while over- production results in defective reticuloendothelial iron release and iron absorption. Design and Methods We studied a Sardinian family in which microcytic anemia due to defective iron absorption and utilization is inherited as a recessive character. Five members showed iron deficiency anemia that was not responsive to oral iron and only partially responsive to parenteral iron administra- tion. To investigate the involvement of known genes implicated in iron metabolism we carried out linkage analysis with microsatellite markers mapping close to these genes. Afterwards, a genome-wide search was performed. Results No linkage was found between the phenotype of the patients and several known human genes involved in iron metabolism (DMT1, TF, TFRC, ZIRTL, HAMP, HJV). Genome-wide scanning by microsatellites and single nucleotide polymorphisms showed a multipoint LOD score of 5.6 on chromosome 22q12.3-13.1, where the matriptase-2 (also known as transmembrane protease, serine 6 or TMPRSS6) gene is located. Its murine counterpart (Tmprss6) has recently been found to be an essential component of a pathway that detects iron deficiency and suppresses hepcidin production. Sequencing analysis of TMPRSS6 revealed a homozygous causal muta- tion, predicting a splicing error and a truncated TMPRSS6 protein in affected members. Homozygous subjects had inappropriately elevated levels of serum and urinary hepcidin. Conclusions The findings of this study suggest that the observed TMPRSS6 mutation leads to overproduc- tion of hepcidin and, in turn, to defective iron absorption and utilization. More generally, they confirm in humans the inhibitory effect of matriptase-2 on hepcidin synthesis already demon- strated in mice. (literal)

Prodotto di

• Meccanismi patogenetici alla base di malattie sindromiche (ME.P05.009.001) (Modulo)
• Utilizzo della popolazione sarda, per la sua omogeneità, per lo studio delle basi genetiche dell'asma allergico (ME.P07.006.002) (Modulo)
• Istituto di Ricerca Genetica e Biomedica (IRGB) (Istituto)

Autore CNR

• ANTONIO CAO (Unità di personale interno)
• GABRIELLA SOLE (Persona)

Insieme di parole chiave

• Keywords of "A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron." (Insieme di parole chiave)

Incoming links:

Autore CNR di

• GABRIELLA SOLE (Persona)
• ANTONIO CAO (Unità di personale interno)

Prodotto

• Istituto di Ricerca Genetica e Biomedica (IRGB) (Istituto)
• Meccanismi patogenetici alla base di malattie sindromiche (ME.P05.009.001) (Modulo)
• Utilizzo della popolazione sarda, per la sua omogeneità, per lo studio delle basi genetiche dell'asma allergico (ME.P07.006.002) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Haematologica (Rivista)

Insieme di parole chiave di

• Keywords of "A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron." (Insieme di parole chiave)