Absence of Neutropenia in Patients With Early Exon Nonsense Mutations in ELANE : Clinical Evidence to Support Gene Therapy Approaches for Severe Congenital Neutropenia.
| Autor: | Joos M; Dana-Farber and Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston., Chang TH; Dana-Farber and Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston., Shimamura A; Dana-Farber and Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston., Newburger PE; Dana-Farber and Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston.; Departments of Pediatrics and of Molecular, Cell and Cancer Biology, UMass Chan Medical School, Worcester, MA. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of pediatric hematology/oncology [J Pediatr Hematol Oncol] 2024 Aug 01; Vol. 46 (6), pp. e463-e465. Date of Electronic Publication: 2024 Jun 25. |
| DOI: | 10.1097/MPH.0000000000002908 |
| Abstrakt: | Severe congenital neutropenia is an inherited bone marrow failure disorder characterized by profoundly low neutrophil counts and promyelocytic maturation arrest in bone marrow. Severe congenital neutropenia is most often caused by heterozygous ELANE mutations. In vitro and mouse xenograft studies using CRISPR/Cas9 have shown that introduction of frameshift/nonsense mutations in mutant ELANE may restore neutrophil counts, providing a model for gene therapy. Here, we present 2 children with inherited nonsense mutations in ELANE analogous to those proposed for gene therapy. Their normal peripheral blood neutrophil counts provide support for this approach through human "experiments of nature." Competing Interests: The authors declare no conflict of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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