Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 1;15(1):8.
doi: 10.1038/s41408-025-01216-w.

CALRins5-mediated clonal hematopoiesis causes severe hemolytic anemia in a female PGK1Ser320Asn carrier

M L Morales #  1   2 , H Cano #  1 , B de la Morena-Barrio  1   3 , J L Vives-Corrons  4 , E J Cuenca-Zamora  1   2   3 , P Garrido-Rodríguez  1   3 , C Bento  5 , J Pereira  5 , J Martínez Nieto  6 , T H Chen-Liang  1 , J L Fuster  7 , S Caracena  1 , M L Lozano  1   3 , R Teruel-Montoya  1   2   3 , J Corral  1   3 , F Ferrer-Marín  8   9   10
Affiliations

CALRins5-mediated clonal hematopoiesis causes severe hemolytic anemia in a female PGK1Ser320Asn carrier

M L Morales et al. Blood Cancer J. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interests: BMB is a co-founder of Longseq Applications S.L. but declares that the research was conducted in the absence of any potential conflict of interest. Ethics approval and consent to participate: The present study was reviewed and approved by the Clinical Research Ethics Committee of the Hospital Universitario Morales Meseguer (EST: 11/21). The patient and her family provided written informed consent in accordance with the Declaration of Helsinki.

Figures

Fig. 1
Fig. 1. Evolution of hemogram parameters, family history, and bone marrow characteristics of the propositus.
A Hemoglobin (g/dL), platelets (103/µL), LDH (U/L), and bilirubin (mg/dL) levels of the propositus are shown over a 6-year period (June/2017–February/2023). The time of diagnosis of essential thrombocythemia (ET) is indicated. B Pedigree showing the presence of the PGK1 p.Ser320Asn variant in family members. C Bone marrow aspirate of the propositus (II.1) at admission showing marked hypercellularity with hyperplasia of megakaryocytes (top), characteristically enlarged, mature, with hyperlobulated nuclei (middle), along with erythroid hyperplasia (bottom). The dashed line indicates an enriched zone in megakaryocytes within the cell clump.
Fig. 2
Fig. 2. Functional and genetic characterization of peripheral blood samples from the two female carriers of the PGK1 mutation.
A Enzymopathies-related enzyme activity levels of phosphoglycerate kinase 1 (PGK1), glucose-6-phosphate dehydrogenase (G6PD), hexokinase (HK), and pyruvate kinase (PK) were quantified. This table also shows the number of reticulocytes in the propositus (II.1) and her mother (I.2). Note that the PGK1 activity in the propositus (near the lower limit of the normal range), together with the severe reticulocytosis, supports a PGK1 deficiency. B Osmoscan profiles in the mother (I.2) and the propositus (II.1) using a Laser-Assisted Optical Rotation Cell Analyzer (LoRRca). The osmotic gradient ektacytometry (OGE) reflects the deformability of erythrocytes measured in a suspension medium with constant shear stress and a variable osmolality. Informative parameters of this curve are shown in Table S2. C CALRins5 identification, quantification of VAF and mRNA levels of mutated and wild-type PGK1 alleles in the CD3+ and CD15 + PB population of the mother (I.2) and the propositus (II.1). D X-chromosome inactivation ratio (269:279) by HUMARA assay in CD3+ and CD15 + PB maternal (I.2) and propositus (II.1) populations. The following reference limits were established: normal, <80:20; moderate deviation, 80:20–90:10; and marked deviation, >90:10. E Methylation studies of unmanipulated genomic DNA from myeloid progenitors. The CpG island of the PGK1 promoter is shown in green. Methylated bases are shown in red, while unmethylated bases are shown in blue. Single nucleotide variant (SNV) positions are marked in blue. The yellow line indicates the position of the PGK1 p.Ser320Asn variant. The two alleles differentiated by phasing are indicated. PGK1 p.Ser320Asn variant is detected in allele 1.
See this image and copyright information in PMC

References

    1. Beutler E. PGK deficiency. Br J Haematol. 2007;136:3–11. - DOI - PubMed
    1. Sakaue S, Kasai T, Mizuta I, Suematsu M, Osone S, Azuma Y, et al. Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism? NPJ Parkinsons Dis. 2017;3:13. - DOI - PMC - PubMed
    1. Chiarelli LR, Morera SM, Bianchi P, Fermo E, Zanella A, Galizzi A, et al. Molecular insights on pathogenic effects of mutations causing phosphoglycerate kinase deficiency. PLoS ONE. 2012;7:e32065. - DOI - PMC - PubMed
    1. Svaasand EK, Aasly J, Landsem VM, Klungland H. Altered expression of PGK1 in a family with phosphoglycerate kinase deficiency. Muscle Nerve. 2007;36:679–84. - DOI - PubMed
    1. Gutierrez E, Bayes MG, Mallick J, Dell’osso L, Lyapichev KA, Muthukumar A. Recognition of a novel variant of phosphoglycerate kinase 1 deficiency PGK1 Galveston (c.472G > C) in a child with hemolytic anemia, neurologic dysfunction and myopathy. Pediatr Hematol Oncol. 2023;40:76–85. - DOI - PubMed

LinkOut - more resources