TY - JOUR
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.
N1 - Publisher Copyright:
Copyright © 2011 by The American Society of Hematology; all rights reserved.
PY - 2014/10/30
Y1 - 2014/10/30
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2014-08-591370
DO - 10.1182/blood-2014-08-591370
M3 - Article
C2 - 25193871
AN - SCOPUS:84908584244
SN - 0006-4971
VL - 124
SP - 2867
EP - 2871
JO - Blood
JF - Blood
IS - 18
ER -