Details

Autor(en) / Beteiligte

• Hildick-Smith, Gordon J.
• Cooney, Jeffrey D.
• Garone, Caterina
• Kremer, Laura S.
• Haack, Tobias B.
• Thon, Jonathan N.
• Miyata, Non
• Lieber, Daniel S.
• Calvo, Sarah E.
• Akman, H. Orhan
• Yien, Yvette Y.
• Huston, Nicholas C.
• Branco, Diana S.
• Shah, Dhvanit I.
• Freedman, Matthew L.
• Koehler, Carla M.
• Italiano, Joseph E.
• Merkenschlager, Andreas
• Beblo, Skadi
• Strom, Tim M.
• Meitinger, Thomas
• Freisinger, Peter
• Donati, M. Alice
• Prokisch, Holger
• Mootha, Vamsi K.
• DiMauro, Salvatore
• Paw, Barry H.

Titel

Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4

Ist Teil von

• American journal of human genetics, 2013-11, Vol.93 (5), p.906-914

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.