A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia

Daniel A. Lichtenstein, Andrew W. Crispin, Anoop K. Sendamarai, Dean R. Campagna, Klaus Schmitz-Abe, Cristovao M. Sousa, Martin D. Kafina, Paul J. Schmidt, Charlotte M. Niemeyer, John Porter, Alison May, Mrinal M Patnaik, Matthew M. Heeney, Alec Kimmelman, Sylvia S. Bottomley, Barry H. Paw, Kyriacos Markianos, Mark D. Fleming

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1913-1917
Number of pages5
JournalBlood
Volume128
Issue number15
StatePublished - Oct 13 2016

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ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Lichtenstein, D. A., Crispin, A. W., Sendamarai, A. K., Campagna, D. R., Schmitz-Abe, K., Sousa, C. M., Kafina, M. D., Schmidt, P. J., Niemeyer, C. M., Porter, J., May, A., Patnaik, M. M., Heeney, M. M., Kimmelman, A., Bottomley, S. S., Paw, B. H., Markianos, K., & Fleming, M. D. (2016). A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia. Blood, 128(15), 1913-1917.