Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4

Gordon J. Hildick-Smith, 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, Andreas Merkenschlager, Skadi Beblo, Tim M. StromThomas Meitinger, Peter Freisinger, M. Alice Donati, Holger Prokisch, Vamsi K. Mootha, Salvatore DiMauro, Barry H. Paw

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)906-914
Number of pages9
JournalAmerican journal of human genetics
Issue number5
Publication statusPublished - Nov 7 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4'. Together they form a unique fingerprint.

Cite this