2. Academic Validation
  3. Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4

Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4

  • Am J Hum Genet. 2013 Nov 7;93(5):906-14. doi: 10.1016/j.ajhg.2013.09.011.
Gordon J Hildick-Smith 1,  Jeffrey D Cooney,  Caterina Garone,  Laura S Kremer,  Tobias B Haack,  Jonathan N Thon,  Non Miyata,  Daniel S Lieber,  Sarah E Calvo,  H Orhan Akman,  Yvette Y Yien,  Nicholas C Huston,  Diana S Branco,  Dhvanit I Shah,  Matthew L Freedman,  Carla M Koehler,  Joseph E Italiano Jr,  Andreas Merkenschlager,  Skadi Beblo,  Tim M Strom,  Thomas Meitinger,  Peter Freisinger,  M Alice Donati,  Holger Prokisch,  Vamsi K Mootha,  Salvatore DiMauro,  Barry H Paw
Affiliations

Affiliation

  • 1 Division of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
PMID: 24119684 DOI: 10.1016/j.ajhg.2013.09.011
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.

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