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 Watson, Morten H Dziegiel, Matthew M Heeney, Alison May, Sylvia S Bottomley, Dorine W Swinkels, Kyriacos Markianos, Elizabeth A Craig, Mark D Fleming
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...
December 17, 2015: Blood