PUBLICATION

Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4

Authors
Hildick-Smith, G.J., Cooney, J.D., Garone, C., Kremer, L.S., Haack, T.B., Thon, J.N., Miyata, N., Lieber, D.S., Calvo, S.E., Akman, H.O., Yien, Y.Y., Huston, N.C., Branco, D.S., Shah, D.I., Freedman, M.L., Koehler, C.M., Italiano, J.E., Merkenschlager, A., Beblo, S., Strom, T.M., Meitinger, T., Freisinger, P., Donati, M.A., Prokisch, H., Mootha, V.K., Dimauro, S., and Paw, B.H.
ID
ZDB-PUB-131018-1
Date
2013
Source
American journal of human genetics   93(5): 906-14 (Journal)
Registered Authors
Koehler, Carla, Paw, Barry, Shah, Dhvanit I.
Keywords
none
MeSH Terms
  • Adolescent
  • Anemia, Macrocytic/genetics*
  • Animals
  • Child
  • Erythropoiesis/genetics
  • Exome
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins/genetics*
  • Mitochondrial Diseases/genetics*
  • Mitochondrial Proteins/genetics
  • Mutation
  • Zebrafish/genetics
PubMed
24119684 Full text @ Am. J. Hum. Genet.
Abstract

We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping