Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA).
Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.
Finberg
Karin E
KE
Pathology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Heeney
Matthew M
MM
Campagna
Dean R
DR
Aydinok
Yeşim
Y
Pearson
Howard A
HA
Hartman
Kip R
KR
Mayo
Mary M
MM
Samuel
Stewart M
SM
Strouse
John J
JJ
Markianos
Kyriacos
K
Andrews
Nancy C
NC
Fleming
Mark D
MD
D000293:Adolescent; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D018095:Germ-Line Mutation; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007223:Infant; D007501:Iron / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics*
D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human