BACKGROUND: The molecular cause of severe congenital neutropenia (SCN) is unknown in 30% to 50% of patients. SEC61A1 encodes the α-subunit of the Sec61 complex, which governs endoplasmic reticulum protein transport and passive calcium leakage. Recently, mutations in SEC61A1 were reported to be pathogenic in common variable immunodeficiency and glom...
Published in The Journal of allergy and clinical immunology
The molecular cause of severe congenital neutropenia (SCN) is unknown in 30% to 50% of patients. SEC61A1 encodes the α-subunit of the Sec61 complex, which governs endoplasmic reticulum protein transport and passive calcium leakage. Recently, mutations in SEC61A1 were reported to be pathogenic in common variable immunodeficiency and glomerulocystic ...
Published in Annals of hematology
Patients with the pre-leukemia bone marrow failure syndrome called severe congenital neutropenia (CN) have an approximately 15% risk of developing acute myeloid leukemia (AML; called here CN/AML). Most CN/AML patients co-acquire CSF3R and RUNX1 mutations, which play cooperative roles in the development of AML. To establish an in vitro model of leuk...
Published in International Journal of Clinical Pediatric Dentistry
VPS45-associated severe congenital neutropenia type V (VPS45-associated SCN5) is an autosomal recessive disorder caused by defective endosomal intracellular protein trafficking due to mutations in VPS45 underlies a reduced absolute neutrophil count >500 cells/mm3 and impaired neutrophil function. VPS45-associated SCN5 is a very rare condition with ...
Published in Clinical immunology (Orlando, Fla.)
Severe congenital neutropenia caused by ELANE gene mutation is a rare disease. To date, only four families were reported with mosaicism. Here we examined the morphology and function of granulocytes isolated from two patients and their mosaic fathers. Analysis of granulocytes isolated from the fathers revealed no genetic mutations. DNA extracted fro...
Published in Journal of Clinical Immunology
PurposeWe report normal neutrophil count in a mother, who carries the same ELANE mutation as her daughter with severe congenital neutropenia. We hypothesized that the mother possessed wild- and mutant-type clones and the wild-type clones could generate neutrophils, whereas the mutant clones could not.MethodsWe confirmed mutant variant ratio by sequ...
Published in Current opinion in hematology
The development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia is now the major cause of mortality. Treatment options are limited and there are no effective prevention strategies. This review focuses on mechanisms of leukemic transformation in severe congenital neutropenia (SCN) and Shwac...
Published in Turkish journal of haematology : official journal of Turkish Society of Haematology
CKN’de, pluripotent hematopoietik kök hücreler ve nötropenik olmayan ebeveynleri genetik bozukluktan bağımsız olarak etkilenirler.
Published in Seminars in cell & developmental biology
Splicing is a ubiquitous process in eukaryotic cells, long recognised as contributing to diversity of the transcriptome. More specifically, splicing fine-tunes the transcriptome output for highly individual outcomes at different stages of cell development, in specific timeframes, which when perturbed result in significant human diseases. Granulopoi...
Published in Journal of Clinical Immunology
PurposeHomozygous mutations in the HAX1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN). There are limited data on cases of gonadal insufficiency that involve the HAX1 gene mutation. We aimed to evaluate the pubertal development and gonadal functions of our patients with a p.Trp44X mutation in the HAX1 gene.MethodPuber...
