Absence of Neutropenia in Patients With Early Exon Nonsense Mutations in ELANE: Clinical Evidence to Support Gene Therapy Approaches for Severe Congenital Neutropenia

被引：0

作者：

Joos, Margret ^{[1
]}

Chang, Timothy H. ^{[1
]}

Shimamura, Akiko ^{[1
]}

Newburger, Peter E. ^{[1
,2
]}

机构：

[1] Harvard Med Sch, Dana Farber Boston Childrens Canc & Blood Disorder, Boston, MA 02115 USA

[2] UMass Chan Med Sch, Dept Pediat & Mol, Cell & Canc Biol, Worcester, MA 01655 USA

来源：

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY | 2024年 / 46卷 / 06期

关键词：

ELANE; gene therapy; severe congenital neutropenia; nonsense mutation; OUTCOMES; BLOOD;

D O I：

10.1097/MPH.0000000000002908

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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."

引用

页码：e463 / e465

页数：3

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