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. © 2013 by The American Society of Human Genetics. All rights reserved.
Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4 / 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 Jr. J.E.; Merkenschlager A.; Beblo S.; Strom T.M.; Meitinger T.; Freisinger P.; Donati M.A.; Prokisch H.; Mootha V.K.; DiMauro S.; Paw B.H.. - In: AMERICAN JOURNAL OF HUMAN GENETICS. - ISSN 0002-9297. - STAMPA. - 93:5(2013), pp. 906-914. [10.1016/j.ajhg.2013.09.011]
Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4
Garone C.;
2013
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. © 2013 by The American Society of Human Genetics. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
