@article{613c441971fc4a13a1d42a01f51aadc5,
title = "Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4",
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.",
author = "Hildick-Smith, {Gordon J.} and Cooney, {Jeffrey D.} and Caterina Garone and Kremer, {Laura S.} and Haack, {Tobias B.} and Thon, {Jonathan N.} and Non Miyata and Lieber, {Daniel S.} and Calvo, {Sarah E.} and Akman, {H. Orhan} and Yien, {Yvette Y.} and Huston, {Nicholas C.} and Branco, {Diana S.} and Shah, {Dhvanit I.} and Freedman, {Matthew L.} and Koehler, {Carla M.} and Italiano, {Joseph E.} and Andreas Merkenschlager and Skadi Beblo and Strom, {Tim M.} and Thomas Meitinger and Peter Freisinger and Donati, {M. Alice} and Holger Prokisch and Mootha, {Vamsi K.} and Salvatore DiMauro and Paw, {Barry H.}",
note = "Funding Information: We are indebted to the individuals described in our study and families for their participation. We thank members of our respective labs (Caiyong Chen and Jacky Chung) and Samuel E. Lux IV, H. Franklin Bunn, David G. Nathan, and Ellis J. Neufeld for critical feedback on the manuscript. We thank Leonard Zon for the Tg(globin-LCR:eGFP) transgenic line, Karin Hoffmeister for the use of the fluorescence-activated cell sorting machine, Caiyong Chen for protein technical advice, Ramiro Massol for confocal microscopy imaging, and Christian Lawrence and his team for the zebrafish husbandry. Fluorescence confocal microscopy was performed at the Harvard Digestive Disease Center Imaging Facility (Boston Children{\textquoteright}s Hospital). This work was supported by grants from the American Heart Association (J.D.C.), the American Society of Hematology (G.J.H.-S., J.D.C.), Cooley{\textquoteright}s Anemia Foundation (D.I.S.), the March of Dimes Foundation (6-FY09-289, B.H.P.), Coordena{\c c}{\~a}o de Aperfeicoamento de Pessoal de N{\'i}vel Superior and Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (D.S.B.), GENOMIT (H.P.), the Marriott Mitochondrial Disorders Clinical Research Fund (V.K.M., S.D.), MEET (H.P.), MitoNET (H.P.), and the National Institutes of Health (K01 DK085217, D.I.S.; T32 HL007574 and F32 DK098866, Y.Y.Y.; R01 GM61721, C.M.K.; R01 GM097136, V.K.M.; P01 HD032062, S.D.M.; R01 DK070838 and P01 HL032262, B.H.P.). ",
year = "2013",
month = nov,
day = "7",
doi = "10.1016/j.ajhg.2013.09.011",
language = "English",
volume = "93",
pages = "906--914",
journal = "American journal of human genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",
}