Pathophysiology and genetic mutations in congenital sideroblastic anemia

Fujiwara, Tohru; Harigae, Hideo

doi:10.1111/ped.12217

Cited by 44 publications

(36 citation statements)

References 35 publications

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“…The mutation was shown by RT-PCR to interfere with correct splicing. Sideroblastic anemias (SAs) are a group of heterogeneous congenital and acquired disorders that have common features of mitochondrial iron accumulation in bone marrow erythroid precursors (ringed sideroblasts), ineffective erythropoiesis, increased levels of tissue iron and varying amounts of hypochromic erythrocytes in the peripheral blood [258, 259]. Congenital sideroblastic anemia is a rare disease caused by mutations of genes involved in heme biosynthesis, Fe-S cluster biogenesis, and mitochondrial protein synthesis (Pearson marrow- pancreas syndrome or PMPS).…”

Section: Mutations In Glrx5 Cause Sideroblastic Anemia or Variant Nonmentioning

confidence: 99%

Iron –sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery

Maio

Rouault

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

175

178

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Iron-sulfur (Fe-S) clusters are ancient, ubiquitous cofactors composed of iron and inorganic sulfur. The combination of the chemical reactivity of iron and sulfur, together with many variations of cluster composition, oxidation states and protein environments, enables Fe-S clusters to participate in numerous biological processes. Fe-S clusters are essential to redox catalysis in nitrogen fixation, mitochondrial respiration and photosynthesis, to regulatory sensing in key metabolic pathways (i. e. cellular iron homeostasis and oxidative stress response), and to the replication and maintenance of the nuclear genome. Fe-S cluster biogenesis is a multistep process that involves a complex sequence of catalyzed protein- protein interactions and coupled conformational changes between the components of several dedicated multimeric complexes. Intensive studies of the assembly process have clarified key points in the biogenesis of Fe-S proteins. However several critical questions still remain, such as: what is the role of frataxin? Why do some defects of Fe-S cluster biogenesis cause mitochondrial iron overload? How are specific Fe-S recipient proteins recognized in the process of Fe-S transfer? This review focuses on the basic steps of Fe-S cluster biogenesis, drawing attention to recent advances achieved on the identification of molecular features that guide selection of specific subsets of nascent Fe-S recipients by the cochaperone HSC20. Additionally, it outlines the distinctive phenotypes of human diseases due to mutations in the components of the basic pathway.

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Section: Mutations In Glrx5 Cause Sideroblastic Anemia or Variant Nonmentioning

confidence: 99%

Iron –sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery

Maio

Rouault

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

175

178

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“…Alteration of bacterial rRNA pseudouridylation affects antibiotic sensitivity (Toh and Mankin, 2008), ablation of rRNA pseudouridylation by CBF5 deletion in S. cerevisae is lethal (Jiang et al, 1993; Zebarjadian et al, 1999), and defects in DKC1/Dyskerin, the mammalian CBF5 ortholog, cause dyskeratosis congenita (Heiss et al, 1998), a disorder characterized by failure of ribosome biogenesis and an increased risk of cancer (Hoareau-Aveilla et al, 2008). Furthermore, deletion of S. cerevisiae PUS1 results in growth defects, and mutation of human PUS1 leads to mitochondrial myopathy and sideroblastic anemia (Fujiwara and Harigae, 2013). …”

Section: Introductionmentioning

confidence: 99%

Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA

Schwartz

Bernstein

Mumbach

et al. 2014

Cell

832

1,074

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SUMMARY Pseudouridine is the most abundant RNA modification, yet except for a few well-studied cases, little is known about the modified positions and their function(s). Here, we develop Ψ-seq for transcriptome-wide quantitative mapping of pseudouridine. We validate Ψ-seq with spike-ins and de novo identification of previously reported positions and discover hundreds of novel sites in human and yeast mRNAs and snoRNAs. Perturbing pseudouridine synthases (PUSs) uncovers which PUSs modify each site and their target sequence features. mRNA pseudouridinylation depends on both site-specific and snoRNA-guided PUSs. Upon heat shock in yeast, Pus7-mediated pseudouridylation is induced at >200 sites and Pus7 deletion decreases the levels of otherwise pseudouridylated mRNA, suggesting a role in enhancing transcript stability. rRNA pseudouridine stoichiometries are conserved, but reduced in cells from dyskeratosis congenita patients, where the PUS DKC1 is mutated. Our work identifies an enhanced, transcritome-wide scope for pseudouridine, and methods to dissect its underlying mechanisms and function.

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“…Congenital sideroblastic anemia has also been described in association with sporadic single mtDNA deletions in Pearson's syndrome (Fujiwara and Harigae 2013) and more recently in a patient with an mtDNA point mutation in ATP6 gene (Burrage et al 2014).…”

Section: Introductionmentioning

confidence: 99%

A Novel Homozygous YARS2 Mutation in Two Italian Siblings and a Review of Literature

Ardissone

Lamantea²,

Quartararo

et al. 2014

JIMD Reports

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YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase that catalyzes the covalent binding of tyrosine to its cognate mt-tRNA. Mutations in YARS2 have been identified in patients with myopathy, lactic acidosis, and sideroblastic anemia type 2 (MLASA2). We report here on two siblings with a novel mutation and a review of literature. The older patient presented at 2 months with marked anemia and lactic acidemia. He required periodic blood transfusions until 14 months of age. Cognitive and motor development was normal. His younger sister was diagnosed at birth, presenting with anemia and lactic acidosis at 1 month of age requiring periodical transfusions. She is now 14 months old and doing well. For both our patients, there was no clinical evidence of muscle involvement. We found a new homozygous mutation in YARS2, located in the a-anticodon-binding (aACB) domain, involved in the interaction with the anticodon of the cognate mt-tRNA Tyr .Our study confirms that MLASA must be considered in patients with congenital sideroblastic anemia and underlines the importance of early diagnosis and supportive therapy in order to prevent severe complications. Clinical severity is variable among YARS2-reported patients: our review of the literature suggests a possible phenotype-genotype correlation, although this should be confirmed in a larger population.

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Pathophysiology and genetic mutations in congenital sideroblastic anemia

Cited by 44 publications

References 35 publications

Iron –sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery

Iron –sulfur cluster biogenesis in mammalian cells: New insights into the molecular mechanisms of cluster delivery

Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA

A Novel Homozygous YARS2 Mutation in Two Italian Siblings and a Review of Literature

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