TY - JOUR
T1 - A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia
AU - Lichtenstein, Daniel A.
AU - Crispin, Andrew W.
AU - Sendamarai, Anoop K.
AU - Campagna, Dean R.
AU - Schmitz-Abe, Klaus
AU - Sousa, Cristovao M.
AU - Kafina, Martin D.
AU - Schmidt, Paul J.
AU - Niemeyer, Charlotte M.
AU - Porter, John
AU - May, Alison
AU - Patnaik, Mrinal M.
AU - Heeney, Matthew M.
AU - Kimmelman, Alec
AU - Bottomley, Sylvia S.
AU - Paw, Barry H.
AU - Markianos, Kyriacos
AU - Fleming, Mark D.
N1 - Publisher Copyright:
© 2016 by The American Society of Hematology.
PY - 2016/10/13
Y1 - 2016/10/13
N2 - The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited blood disorders characterized by pathological mitochondrial iron deposition in erythroid precursors. Each known cause has been attributed to a mutation in a protein associated with heme biosynthesis, iron-sulfur cluster biogenesis, mitochondrial translation, or a component of the mitochondrial respiratory chain. Here, we describe a recurring mutation, c.276_278del, p.F93del, in NDUFB11, a mitochondrial respiratory complex I-associated protein encoded on the X chromosome, in 5 males with a variably syndromic, normocytic CSA. The p.F93del mutation results in respiratory insufficiency and loss of complex I stability and activity in patient-derived fibroblasts. Targeted introduction of this allele into K562 erythroleukemia cells results in a proliferation defect with minimal effect on erythroid differentiation potential, suggesting the mechanism of anemia in this disorder.
AB - The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited blood disorders characterized by pathological mitochondrial iron deposition in erythroid precursors. Each known cause has been attributed to a mutation in a protein associated with heme biosynthesis, iron-sulfur cluster biogenesis, mitochondrial translation, or a component of the mitochondrial respiratory chain. Here, we describe a recurring mutation, c.276_278del, p.F93del, in NDUFB11, a mitochondrial respiratory complex I-associated protein encoded on the X chromosome, in 5 males with a variably syndromic, normocytic CSA. The p.F93del mutation results in respiratory insufficiency and loss of complex I stability and activity in patient-derived fibroblasts. Targeted introduction of this allele into K562 erythroleukemia cells results in a proliferation defect with minimal effect on erythroid differentiation potential, suggesting the mechanism of anemia in this disorder.
UR - http://www.scopus.com/inward/record.url?scp=84991582039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991582039&partnerID=8YFLogxK
U2 - 10.1182/blood-2016-05-719062
DO - 10.1182/blood-2016-05-719062
M3 - Article
C2 - 27488349
AN - SCOPUS:84991582039
SN - 0006-4971
VL - 128
SP - 913
EP - 917
JO - Blood
JF - Blood
IS - 15
ER -