ArticleBlood2013
Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
- Current view on the etiopathogenesis of aplastic anemia.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Article
- LMAN1 serves as a cargo receptor for thrombopoietin.JCI insight · 2024Article
- A Rare THPO Gene Mutation in a Saudi Female Child: A Case Report and Literature Review.Cureus · 2024Article
- Deciphering the differential impact of thrombopoietin/MPL signaling on hematopoietic stem/progenitor cell function in bone marrow and spleen.Stem cell reports · 2024Article
- Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.Nature communications · 2024Article
- Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management.Journal of clinical medicine · 2023Review
- Defective binding of ETS1 and STAT4 due to a mutation in the promoter region ofHaematologica · 2023Article
- The name counts: the case of 'congenital amegakaryocytic thrombocytopenia'.Haematologica · 2023Article
- Megakaryocyte Diversity in Ontogeny, Functions and Cell-Cell Interactions.Frontiers in oncology · 2022Article
- Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.Frontiers in oncology · 2022Article
- Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing.Life (Basel, Switzerland) · 2021Review
- CAMT-MPL: congenital amegakaryocytic thrombocytopenia caused by MPL mutations - heterogeneity of a monogenic disorder - a comprehensive analysis of 56 patients.Haematologica · 2021Article
- The thrombopoietin receptor: revisiting the master regulator of platelet production.Platelets · 2021Review
- Thrombocytosis in children and adolescents-classification, diagnostic approach, and clinical management.Annals of hematology · 2021Review
- Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias.Journal of clinical medicine · 2021Review
- Current evidence and the emerging role of eltrombopag in severe aplastic anemia.Therapeutic advances in hematology · 2021Review
- Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia.Blood advances · 2020Article
- Article
- Inherited Thrombocytopenia: Update on Genes and Genetic Variants Which may be Associated With Bleeding.Frontiers in cardiovascular medicine · 2019Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
We recently identified 2 siblings afflicted with idiopathic, autosomal recessive aplastic anemia. Whole-exome sequencing identified a novel homozygous missense mutation in thrombopoietin (THPO, c.112C>T) in both affected siblings. This mutation encodes an arginine to cysteine substitution at residue 38 or residue 17 excluding the 21-amino acid signal peptide of THPO receptor binding domain (RBD). THPO has 4 conserved cysteines in its RBD that form 2 disulfide bonds. Our in silico modeling predicts that introduction of a fifth cysteine may disrupt normal disulfide bonding to cause poor receptor binding. In functional assays, the mutant-THPO-containing media shows two- to threefold reduced ability to sustain UT7-TPO cells, which require THPO for proliferation. Both parents and a sibling with heterozygous R17C change have reduced platelet counts, whereas a sibling with wild-type sequence has normal platelet count. Thus, the R17C partial loss-of-function allele results in aplastic anemia in the homozygous state and mild thrombocytopenia in the heterozygous state in our family. Together with the recent identification of THPO receptor (MPL) mutations and the effects of THPO agonists in aplastic anemia, our results have clinical implications in the diagnosis and treatment of patients with aplastic anemia and highlight a role for the THPO-MPL pathway in hematopoiesis in vivo.
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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.