Inherited biallelic CSF3R mutations in severe congenital neutropenia.

Autor:	Triot A; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Järvinen PM; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Arostegui JI; Immunology Department, Hospital Clínic, Barcelona, Spain;, Murugan D; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Kohistani N; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Dapena Díaz JL; Department of Pediatric Oncology-Hematology, Maternal-Infant Hospital Vall d'Hebron, Barcelona, Spain;, Racek T; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Puchałka J; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Gertz EM; Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD;, Schäffer AA; Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD;, Kotlarz D; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;, Pfeifer D; Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, Germany;, Díaz de Heredia Rubio C; Department of Pediatric Oncology-Hematology, Maternal-Infant Hospital Vall d'Hebron, Barcelona, Spain;, Ozdemir MA; Division of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey; and., Patiroglu T; Division of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey; and., Karakukcu M; Division of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey; and., Sánchez de Toledo Codina J; Department of Pediatric Oncology-Hematology, Maternal-Infant Hospital Vall d'Hebron, Barcelona, Spain;, Yagüe J; Immunology Department, Hospital Clínic, Barcelona, Spain;, Touw IP; Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands., Unal E; Division of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey; and., Klein C; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany;
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2014 Jun 12; Vol. 123 (24), pp. 3811-7. Date of Electronic Publication: 2014 Apr 21.
DOI:	10.1182/blood-2013-11-535419
Abstrakt:	Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis. (© 2014 by The American Society of Hematology.)
Databáze:	MEDLINE
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