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. Thompson & 15 others Laura 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

*Corresponding author for this work

Research output: Contribution to journalArticle

83 Citations (Scopus)

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

Fingerprint

Fever
Mutation
Saccharomycetales
Mitochondria
Gene encoding
Mitochondrial Proteins
Transfer RNA
Heme
Sulfur
Cytosol
Yeast
B-Lymphocytes
Iron
Cells
Genes
Proteins
X-linked sideroblastic anemia
mitochondrial RNA
tRNA nucleotidyltransferase

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., ... 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
Chakraborty, Pranesh K. ; Schmitz-Abe, Klaus ; Kennedy, Erin K. ; Mamady, Hapsatou ; Naas, Turaya ; Durie, Danielle ; Campagna, Dean R. ; Lau, Ashley ; Sendamarai, Anoop K. ; Wiseman, Daniel H. ; May, Alison ; Jolles, Stephen ; Connor, Philip ; Powell, Colin ; Heeney, Matthew M. ; Giardina, Patricia Jane ; Klaassen, Robert J. ; Kannengiesser, Caroline ; Thuret, Isabelle ; Thompson, Alexis A. ; Marques, Laura ; Hughes, Stephen ; Bonney, Denise K. ; Bottomley, Sylvia S. ; Wynn, Robert F. ; Laxer, Ronald M. ; Minniti, Caterina P. ; Moppett, John ; Bordon, Victoria ; Geraghty, Michael ; Joyce, Paul B.M. ; Markianos, Kyriacos ; Rudner, Adam D. ; Holcik, Martin ; Fleming, Mark D. / Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). In: Blood. 2014 ; Vol. 124, No. 18. pp. 2867-2871.
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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.",
author = "Chakraborty, {Pranesh K.} and Klaus Schmitz-Abe and Kennedy, {Erin K.} and Hapsatou Mamady and Turaya Naas and Danielle Durie and Campagna, {Dean R.} and Ashley Lau and Sendamarai, {Anoop K.} and Wiseman, {Daniel H.} and Alison May and Stephen Jolles and Philip Connor and Colin Powell and Heeney, {Matthew M.} and Giardina, {Patricia Jane} and Klaassen, {Robert J.} and Caroline Kannengiesser and Isabelle Thuret and Thompson, {Alexis A.} and Laura Marques and Stephen Hughes and Bonney, {Denise K.} and Bottomley, {Sylvia S.} and Wynn, {Robert F.} and Laxer, {Ronald M.} and Minniti, {Caterina P.} and John Moppett and Victoria Bordon and Michael Geraghty and Joyce, {Paul B.M.} and Kyriacos Markianos and Rudner, {Adam D.} and Martin Holcik and Fleming, {Mark D.}",
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Chakraborty, PK, Schmitz-Abe, K, Kennedy, EK, Mamady, H, Naas, T, Durie, D, Campagna, DR, Lau, A, Sendamarai, AK, Wiseman, DH, May, A, Jolles, S, Connor, P, Powell, C, Heeney, MM, Giardina, PJ, Klaassen, RJ, Kannengiesser, C, Thuret, I, Thompson, AA, Marques, L, Hughes, S, Bonney, DK, Bottomley, SS, Wynn, RF, Laxer, RM, Minniti, CP, Moppett, J, Bordon, V, Geraghty, M, Joyce, PBM, Markianos, K, Rudner, AD, Holcik, M & Fleming, MD 2014, 'Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)', Blood, vol. 124, no. 18, pp. 2867-2871. https://doi.org/10.1182/blood-2014-08-591370

Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). / Chakraborty, Pranesh K.; Schmitz-Abe, Klaus; Kennedy, Erin K.; Mamady, Hapsatou; Naas, Turaya; Durie, Danielle; Campagna, Dean R.; Lau, Ashley; Sendamarai, Anoop K.; Wiseman, Daniel H.; May, Alison; Jolles, Stephen; Connor, Philip; Powell, Colin; Heeney, Matthew M.; Giardina, Patricia Jane; Klaassen, Robert J.; Kannengiesser, Caroline; Thuret, Isabelle; Thompson, Alexis A.; Marques, Laura; Hughes, Stephen; Bonney, Denise K.; Bottomley, Sylvia S.; Wynn, Robert F.; Laxer, Ronald M.; Minniti, Caterina P.; Moppett, John; Bordon, Victoria; Geraghty, Michael; Joyce, Paul B.M.; Markianos, Kyriacos; Rudner, Adam D.; Holcik, Martin; Fleming, Mark D.

In: Blood, Vol. 124, No. 18, 30.10.2014, p. 2867-2871.

Research output: Contribution to journalArticle

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T1 - Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)

AU - Chakraborty, Pranesh K.

AU - Schmitz-Abe, Klaus

AU - Kennedy, Erin K.

AU - Mamady, Hapsatou

AU - Naas, Turaya

AU - Durie, Danielle

AU - Campagna, Dean R.

AU - Lau, Ashley

AU - Sendamarai, Anoop K.

AU - Wiseman, Daniel H.

AU - May, Alison

AU - Jolles, Stephen

AU - Connor, Philip

AU - Powell, Colin

AU - Heeney, Matthew M.

AU - Giardina, Patricia Jane

AU - Klaassen, Robert J.

AU - Kannengiesser, Caroline

AU - Thuret, Isabelle

AU - Thompson, Alexis A.

AU - Marques, Laura

AU - Hughes, Stephen

AU - Bonney, Denise K.

AU - Bottomley, Sylvia S.

AU - Wynn, Robert F.

AU - Laxer, Ronald M.

AU - Minniti, Caterina P.

AU - Moppett, John

AU - Bordon, Victoria

AU - Geraghty, Michael

AU - Joyce, Paul B.M.

AU - Markianos, Kyriacos

AU - Rudner, Adam D.

AU - Holcik, Martin

AU - Fleming, Mark D.

PY - 2014/10/30

Y1 - 2014/10/30

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