ArticleThe Journal of clinical investigation2019
Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The application of next-generation sequencing technology in congenital haemolytic anaemia: a systematic review and meta-analysis.Clinical and experimental medicine · 2025Pooled it
- Hereditary Spherocytosis: Linking Ion Transport Defects to Osmotic Gradient Ektacytometry Profiles-A Review.International journal of molecular sciences · 2026Review
- Advances on the genetic basis of red cell membrane disorders.Current opinion in hematology · 2025Review
- Synonymous variant at the terminal nucleotide in exon 3 of F7 causes abnormal splicing: A case report.Molecular genetics & genomic medicine · 2024Article
- Current Status of Molecular Diagnosis of Hereditary Hemolytic Anemia in Korea.Journal of Korean medical science · 2024Review
- A single-center cohort study of patients with hereditary spherocytosis in Central Europe reveals a high frequency of novel disease-causing genotypes.HemaSphere · 2024Article
- Endothelial tip/stalk cell selection requires BMP9-induced βMolecular biology of the cell · 2023Article
- Anemia in the pediatric patient.Blood · 2022Article
- The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper.HemaSphere · 2022Article
- Combinatorial Power of cfDNA, CTCs and EVs in Oncology.Diagnostics (Basel, Switzerland) · 2022Review
- Diagnosis and clinical management of red cell membrane disorders.Hematology. American Society of Hematology. Education Program · 2021Article
- Facilitating EMA binding test performance using fluorescent beads combined with next-generation sequencing.EJHaem · 2021Article
- Review
- Molecular heterogeneity of pyruvate kinase deficiency.Haematologica · 2020Review
- Antisense targeting of decoy exons can reduce intron retention and increase protein expression in human erythroblasts.RNA (New York, N.Y.) · 2020Article
- Exome sequencing for diagnosis of congenital hemolytic anemia.Orphanet journal of rare diseases · 2020Article
- Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency.American journal of hematology · 2020Article
- How will next generation sequencing (NGS) improve the diagnosis of congenital hemolytic anemia?Annals of translational medicine · 2020Article
- Clinical Diagnosis of Red Cell Membrane Disorders: Comparison of Osmotic Gradient Ektacytometry and Eosin Maleimide (EMA) Fluorescence Test for Red Cell Band 3 (AE1, SLC4A1) Content for Clinical Diagnosis.Frontiers in physiology · 2020Article
- Anemia lurking in introns.The Journal of clinical investigation · 2019Article
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17 authors at 13 institutions in 3 countries.
Funding
Abstract
The etiology of severe hemolytic anemia in most patients with recessive hereditary spherocytosis (rHS) and the related disorder hereditary pyropoikilocytosis (HPP) is unknown. Whole exome sequencing of DNA from probands of 24 rHS or HPP kindreds identified numerous mutations in erythrocyte membrane α-spectrin (SPTA1). Twenty-eight mutations were novel, with null alleles frequently found in trans to missense mutations. No mutations were identified in a third of SPTA1 alleles (17/48). Whole genome sequencing revealed linkage disequilibrium between the common rHS-linked α-spectrinBug Hill polymorphism and a rare intron 30 variant in all 17 mutation-negative alleles. In vitro minigene studies and in vivo splicing analyses revealed the intron 30 variant changes a weak alternate branch point (BP) to a strong BP. This change leads to increased utilization of an alternate 3' splice acceptor site, perturbing normal α-spectrin mRNA splicing and creating an elongated mRNA transcript. In vivo mRNA stability studies revealed the newly created termination codon in the elongated transcript activates nonsense mediated decay leading to spectrin deficiency. These results demonstrate a unique mechanism of human genetic disease contributes to the etiology of a third of cases of rHS, facilitating diagnosis and treatment of severe anemia, and identifying a new target for therapeutic manipulation.
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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.