scholarly journals Kostmann disease and other forms of severe congenital neutropenia

2021 ◽  
Author(s):  
Bengt Fadeel ◽  
Daniel Garwicz ◽  
Göran Carlsson ◽  
Bengt Sandstedt ◽  
Magnus Nordenskjöld
Keyword(s):  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Kostmann Disease

scholarly journals Hax1 regulates neutrophil adhesion and motility through RhoA

2011 ◽  
Vol 193 (3) ◽  
pp. 465-473 ◽  
Author(s):  
Peter J. Cavnar ◽  
Erwin Berthier ◽  
David J. Beebe ◽  
Anna Huttenlocher
Keyword(s):  
Adaptor Protein ◽  
Neutrophil Function ◽  
Negative Regulator ◽  
Neutrophil Adhesion ◽  
Severe Congenital Neutropenia ◽  
Loss Of Function ◽  
Congenital Neutropenia ◽  
Rhoa Activity ◽  
Protein X ◽  
Kostmann Disease

Kostmann disease is an inherited severe congenital neutropenia syndrome associated with loss-of-function mutations in an adaptor protein HS1-associated protein X-1 (Hax1). How Hax1 regulates neutrophil function remains largely unknown. In this paper, we use ribonucleic acid interference to deplete Hax1 in the neutrophil-like cell line PLB-985 and identify Hax1 as a negative regulator of integrin-mediated adhesion and chemotaxis. Using microfluidics, we show that depletion of Hax1 impairs neutrophil uropod detachment and directed migration. Hax1-deficient cells also display increased integrin-mediated adhesion and reduced RhoA activity. Moreover, depletion of RhoA induces increased neutrophil adhesion and impaired migration, suggesting that Hax1 regulates neutrophil adhesion and chemotaxis through RhoA. Accordingly, activation of RhoA is sufficient to rescue adhesion of Hax1-deficient neutrophils. Together, our findings identify Hax1 as a novel regulator of neutrophil uropod detachment and chemotaxis through RhoA.

A novel missense mutation in theHAX1gene in severe congenital neutropenia patients (Kostmann disease)

2009 ◽  
Vol 76 (6) ◽  
pp. 569-572 ◽  
Author(s):  
M Faiyaz-Ul-Haque ◽  
A Al-Jefri ◽  
HA Abalkhail ◽  
M Toulimat ◽  
MA Al-Muallimi ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Kostmann Disease

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)

2006 ◽  
Vol 39 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Christoph Klein ◽  
Magda Grudzien ◽  
Giridharan Appaswamy ◽  
Manuela Germeshausen ◽  
Inga Sandrock ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Kostmann Disease

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
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