Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)

Pranesh K. Chakraborty, Klaus Schmitz-Abe, Erin K. Kennedy, Hapsatou Mamady, Turaya Naas, Danielle Durie, Dean R. Campagna, Ashley Lau, Anoop K. Sendamarai, Daniel H. Wiseman, Alison May, Stephen Jolles, Philip Connor, Colin Powell, Matthew M. Heeney, Patricia Jane Giardina, Robert J. Klaassen, Caroline Kannengiesser, Isabelle Thuret, Alexis A. ThompsonLaura Marques, Stephen Hughes, Denise K. Bonney, Sylvia S. Bottomley, Robert F. Wynn, Ronald M. Laxer, Caterina P. Minniti, John Moppett, Victoria Bordon, Michael Geraghty, Paul B.M. Joyce, Kyriacos Markianos, Adam D. Rudner, Martin Holcik, Mark D. Fleming

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92 Scopus citations

Abstract

Mutationsingenes encoding proteins that are in volved in mitochondrial heme synthesis, iron-sulfur cluster biogenesis, and mitochondrial protein synthesis have previously been implicated in the pathogenesis of the congenital sideroblastic anemias (CSAs). We recently described a syndromic form of CSA associated with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Here we demonstrate that SIFD is caused by biallelic mutations in TRNT1, the gene encoding the CCA-adding enzyme essential for maturationofboth nuclear and mitochondrial transfer RNAs. Using budding yeast lacking the TRNT1 homolog, CCA1, we confirm that the patient-associated TRNT1 mutations resultin partial lossoffunction of TRNT1 and lead to metabolic defectsinboth the mitochondria and cytosol, which can account for the phenotypic pleiotropy.

Original languageEnglish (US)
Pages (from-to)2867-2871
Number of pages5
JournalBlood
Volume124
Issue number18
DOIs
StatePublished - Oct 30 2014

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Chakraborty, P. K., Schmitz-Abe, K., Kennedy, E. K., Mamady, H., Naas, T., Durie, D., Campagna, D. R., Lau, A., Sendamarai, A. K., Wiseman, D. H., May, A., Jolles, S., Connor, P., Powell, C., Heeney, M. M., Giardina, P. J., Klaassen, R. J., Kannengiesser, C., Thuret, I., ... Fleming, M. D. (2014). Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood, 124(18), 2867-2871. https://doi.org/10.1182/blood-2014-08-591370