| Literature DB >> 25193871 |
Pranesh K Chakraborty1, Klaus Schmitz-Abe2, Erin K Kennedy3, Hapsatou Mamady1, Turaya Naas1, Danielle Durie1, Dean R Campagna4, Ashley Lau4, Anoop K Sendamarai4, Daniel H Wiseman5, Alison May6, Stephen Jolles7, Philip Connor8, Colin Powell9, Matthew M Heeney10, Patricia-Jane Giardina11, Robert J Klaassen12, Caroline Kannengiesser13, Isabelle Thuret14, Alexis A Thompson15, Laura Marques16, Stephen Hughes17, Denise K Bonney5, Sylvia S Bottomley18, Robert F Wynn5, Ronald M Laxer19, Caterina P Minniti20, John Moppett21, Victoria Bordon22, Michael Geraghty12, Paul B M Joyce23, Kyriacos Markianos2, Adam D Rudner3, Martin Holcik24, Mark D Fleming4.
Abstract
Mutations in genes encoding proteins that are involved 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 maturation of both nuclear and mitochondrial transfer RNAs. Using budding yeast lacking the TRNT1 homolog, CCA1, we confirm that the patient-associated TRNT1 mutations result in partial loss of function of TRNT1 and lead to metabolic defects in both the mitochondria and cytosol, which can account for the phenotypic pleiotropy.Entities:
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Year: 2014 PMID： 25193871 PMCID： PMC4215314 DOI： 10.1182/blood-2014-08-591370
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113