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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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

Fingerprint

Iron
Electron Transport Complex I
Mutation
Biosynthesis
Fibroblasts
Chromosomes
Blood Group Antigens
Heme
Sulfur
Leukemia, Erythroblastic, Acute
Chromosomes, Human, Pair 5
Proteins
K562 Cells
X Chromosome
Organelle Biogenesis
Electron Transport
Respiratory Insufficiency
Defects
Anemia
Alleles

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., ... 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.

A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia. / Lichtenstein, Daniel A.; Crispin, Andrew W.; Sendamarai, Anoop K.; Campagna, Dean R.; Schmitz-Abe, Klaus; Sousa, Cristovao M.; Kafina, Martin D.; Schmidt, Paul J.; Niemeyer, Charlotte M.; Porter, John; May, Alison; Patnaik, Mrinal M; Heeney, Matthew M.; Kimmelman, Alec; Bottomley, Sylvia S.; Paw, Barry H.; Markianos, Kyriacos; Fleming, Mark D.

In: Blood, Vol. 128, No. 15, 13.10.2016, p. 1913-1917.

Research output: Contribution to journalArticle

Lichtenstein, DA, Crispin, AW, Sendamarai, AK, Campagna, DR, Schmitz-Abe, K, Sousa, CM, Kafina, MD, Schmidt, PJ, Niemeyer, CM, Porter, J, May, A, Patnaik, MM, Heeney, MM, Kimmelman, A, Bottomley, SS, Paw, BH, Markianos, K & Fleming, MD 2016, 'A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia', Blood, vol. 128, no. 15, pp. 1913-1917.
Lichtenstein DA, Crispin AW, Sendamarai AK, Campagna DR, Schmitz-Abe K, Sousa CM et al. A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia. Blood. 2016 Oct 13;128(15):1913-1917.
Lichtenstein, Daniel A. ; Crispin, Andrew W. ; Sendamarai, Anoop K. ; Campagna, Dean R. ; Schmitz-Abe, Klaus ; Sousa, Cristovao M. ; Kafina, Martin D. ; Schmidt, Paul J. ; Niemeyer, Charlotte M. ; Porter, John ; May, Alison ; Patnaik, Mrinal M ; Heeney, Matthew M. ; Kimmelman, Alec ; Bottomley, Sylvia S. ; Paw, Barry H. ; Markianos, Kyriacos ; Fleming, Mark D. / A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia. In: Blood. 2016 ; Vol. 128, No. 15. pp. 1913-1917.
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