Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4
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 z...
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Published in | American journal of human genetics Vol. 93; no. 5; pp. 906 - 914 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
07.11.2013
Cell Press Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Present address: Universidade Estadual de Campinas, Campinas, São Paulo 13083-970, Brazil These authors contributed equally to this work Present address: University of Texas Health Science Center, San Antonio, TX 78229, USA Present address: Weill Cornell Medical College, New York, NY 10021, USA |
ISSN: | 0002-9297 1537-6605 |
DOI: | 10.1016/j.ajhg.2013.09.011 |