scholarly journals Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia

2020 ◽  
Vol 11 ◽  
Author(s):  
Khanh N. Dinh ◽  
Seth J. Corey ◽  
Marek Kimmel
Keyword(s):  
Selection Coefficient ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Moran Model ◽  
Myeloid Neoplasia

scholarly journals Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Tham Thi Tran ◽  
Quang Van Vu ◽  
Taizo Wada ◽  
Akihiro Yachie ◽  
Huong Le Thi Minh ◽  
...  
Keyword(s):  
Early Onset ◽  
Bacterial Infections ◽  
Complete Blood Count ◽  
Hereditary Diseases ◽  
Severe Neutropenia ◽  
Sequencing Analysis ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Direct Dna Sequencing ◽  
Life Threatening

Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.

scholarly journals Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3

2010 ◽  
Vol 19 (1) ◽  
pp. 18-22 ◽  
Author(s):  
Siddharth Banka ◽  
Elena Chervinsky ◽  
William G Newman ◽  
Yanick J Crow ◽  
Shay Yeganeh ◽  
...  
Keyword(s):  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia

In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 668-670 ◽  
Author(s):  
Manuela Germeshausen ◽  
Karl Welte ◽  
Matthias Ballmaier
Keyword(s):  
Single Cells ◽  
Bone Marrow Failure ◽  
Point Mutations ◽  
Predictive Marker ◽  
Lymphoid Cells ◽  
Lower Percentage ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Bone Marrow Failure Syndrome

Abstract Severe congenital neutropenia (CN) is a rare bone marrow failure syndrome with a high incidence of acute leukemia. In previous studies, we could show that point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R are a highly predictive marker for leukemic development in CN patients. To find out at which stage of hematopoietic development these mutations emerge and how they are propagated during hematopoietic differentiation, we analyzed single cells of different hematopoietic subpopulations from CN patients with CSF3R mutations. We found that CSF3R mutations are not restricted to the myeloid compartment but are also detectable in lymphoid cells, although at a much lower percentage. From our observations, we conclude that CSF3R mutations are acquired in multipotent hematopoietic progenitor cells in CN patients and that they are clonally expanded in myeloid cells expressing the G-CSF receptor due to the growth advantage mediated by the CSF3R mutation.

Heterozygous Variants of CLPB are a Cause of Severe Congenital Neutropenia

Blood ◽  
2021 ◽  
Author(s):  
Julia T Warren ◽  
Ryan R Cupo ◽  
Peeradol Wattanasirakul ◽  
David Spencer ◽  
Adam E Locke ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Binding Pocket ◽  
Dominant Negative ◽  
Neurologic Disease ◽  
Severe Congenital Neutropenia ◽  
Hematopoietic Progenitors ◽  
Granulocytic Differentiation ◽  
Congenital Neutropenia ◽  
Biallelic Mutations ◽  
Methylglutaconic Aciduria

Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Approximately one-third of cases do not have a known genetic cause. Exome sequencing of 104 persons with congenital neutropenia identified heterozygous missense variants of CLPB (caseinolytic peptidase B) in 5 SCN cases, with 5 more cases identified through additional sequencing efforts or clinical sequencing. CLPB encodes an adenosine triphosphatase (ATPase) implicated in protein folding and mitochondrial function. Prior studies showed that biallelic mutations of CLPB are associated with a syndrome of 3-methylglutaconic aciduria, cataracts, neurologic disease, and variable neutropenia. However, 3-methylglutaconic aciduria was not observed and, other than neutropenia, these clinical features were uncommon in our series. Moreover, the CLPB variants are distinct, consisting of heterozygous variants that cluster near the ATP-binding pocket. Both genetic loss of CLPB and expression of CLPB variants results in impaired granulocytic differentiation of human hematopoietic progenitors and increased apoptosis. These CLPB variants associate with wildtype CLPB and inhibit its ATPase and disaggregase activity in a dominant-negative fashion. Finally, expression of CLPB variants is associated with impaired mitochondrial function but does not render cells more sensitive to endoplasmic reticulum stress. Together, these data show that heterozygous CLPB variants are a new and relatively common cause of congenital neutropenia and should be considered in the evaluation of patients with congenital neutropenia.

The Clinical, Immunohematological, and Molecular Study of Iranian Patients with Severe Congenital Neutropenia

2007 ◽  
Vol 27 (5) ◽  
pp. 525-533 ◽  
Author(s):  
Nima Rezaei ◽  
Mostafa Moin ◽  
Zahra Pourpak ◽  
Asghar Ramyar ◽  
Mina Izadyar ◽  
...  
Keyword(s):  
Molecular Study ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Iranian Patients

Hepatic Hemangioendothelioma in an Infant With Severe Congenital Neutropenia

2012 ◽  
Vol 34 (4) ◽  
pp. 298-300 ◽  
Author(s):  
Veronique Dinand ◽  
Satya Prakash Yadav ◽  
Christine Bellanné-Chantelot ◽  
Sunila Jain ◽  
Manorama Bhargava ◽  
...  
Keyword(s):  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia
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