ArticleThe Journal of clinical investigation2015
X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Clinical variability of ATP11C-related hemolytic anemia: expanding the phenotypic and diagnostic spectrum.Blood advances · 2026Article
- A case report of congenital sideroblastic anemia caused by a novel ALAS2 mutation in conjunction with thalassemia.Annals of hematology · 2026Article
- Article
- Article
- Three-generation female cohort with macrocytic anemia and iron overload.American journal of hematology · 2025Article
- Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns.Journal of Zhejiang University. Science. B · 2022Review
- Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.Scientific reports · 2022Article
- Azacitidine is a potential therapeutic drug for pyridoxine-refractory female X-linked sideroblastic anemia.Blood advances · 2022Article
- Identification of Regulatory Factors and Prognostic Markers in Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2022Article
- X-linked sideroblastic anaemia in a female fetus: a case report and a literature review.BMC medical genomics · 2021Review
- SLC25A38 congenital sideroblastic anemia: Phenotypes and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature.Human mutation · 2021Review
- [New mutation of congenital sideroblastic anemia: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Review
- Identification of a novel heterozygous ALAS2 mutation in a young Chinese female with X-linked sideroblastic anemia.Annals of hematology · 2020Article
- Understanding Sideroblastic Anemia: An Overview of Genetics, Epidemiology, Pathophysiology and Current Therapeutic Options.Journal of blood medicine · 2020Review
- Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation.Molecular and cellular biology · 2019Article
- Heterozygous Deletion of theFrontiers in genetics · 2019Article
- Iron metabolism in erythroid cells and patients with congenital sideroblastic anemia.International journal of hematology · 2018Review
- Whole-exome sequencing identifies an α-globin cluster triplication resulting in increased clinical severity of β-thalassemia.Cold Spring Harbor molecular case studies · 2017Article
- Developmentally-faithful and effective human erythropoiesis in immunodeficient and Kit mutant mice.American journal of hematology · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Macrocytic anemia with abnormal erythropoiesis is a common feature of megaloblastic anemias, congenital dyserythropoietic anemias, and myelodysplastic syndromes. Here, we characterized a family with multiple female individuals who have macrocytic anemia. The proband was noted to have dyserythropoiesis and iron overload. After an extensive diagnostic evaluation that did not provide insight into the cause of the disease, whole-exome sequencing of multiple family members revealed the presence of a mutation in the X chromosomal gene ALAS2, which encodes 5'-aminolevulinate synthase 2, in the affected females. We determined that this mutation (Y365C) impairs binding of the essential cofactor pyridoxal 5'-phosphate to ALAS2, resulting in destabilization of the enzyme and consequent loss of function. X inactivation was not highly skewed in wbc from the affected individuals. In contrast, and consistent with the severity of the ALAS2 mutation, there was a complete skewing toward expression of the WT allele in mRNA from reticulocytes that could be recapitulated in primary erythroid cultures. Together, the results of the X inactivation and mRNA studies illustrate how this X-linked dominant mutation in ALAS2 can perturb normal erythropoiesis through cell-nonautonomous effects. Moreover, our findings highlight the value of whole-exome sequencing in diagnostically challenging cases for the identification of disease etiology and extension of the known phenotypic spectrum of disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.