Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9

Klaus Schmitz-Abe, Szymon J. Ciesielski, Paul J. Schmidt, Dean R. Campagna, Fedik Rahimov, Brenda A. Schilke, Marloes Cuijpers, Klaus Rieneck, Birgitte Lausen, Michael L. Linenberger, Anoop K. Sendamarai, Chaoshe Guo, Inga Hofmann, Peter E. Newburger, Dana Matthews, Akiko Shimamura, Pieter J.L.M. Snijders, Meghan C. Towne, Charlotte M. Niemeyer, Henry G. WatsonMorten H. Dziegiel, Matthew M. Heeney, Alison May, Sylvia S. Bottomley, Dorine W. Swinkels, Kyriacos Markianos, Elizabeth A. Craig, Mark D. Fleming*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

64 Citations (Scopus)

Abstract

The congenital sideroblastic anemias (CSAs) are relatively uncommon diseases characterized by defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Here we demonstrate that mutations in HSPA9, a mitochondrial HSP70 homolog located in the chromosome 5q deletion syndrome 5q33 critical deletion interval and involved in mitochondrial Fe-S biogenesis, result in CSA inherited as an autosomal recessive trait. In a fraction of patients with just 1 severe loss-of-function allele, expression of the clinical phenotype is associated with a common coding single nucleotide polymorphism in trans that correlates with reduced messenger RNA expression and results in a pseudodominant pattern of inheritance.

Original languageEnglish
JournalBlood
Volume126
Issue number25
Pages (from-to)2734-2738
ISSN0006-4971
DOIs
Publication statusPublished - 2015

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