Details of Disease

General Information of Disease (ID: DISES99N)

• Disease Name: Severe congenital neutropenia
• Synonyms: neutropenia, severe congenital; SCN; Severe Chronic Neutropenia
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DISZ74WG: Constitutional neutropenia
  DISES99N: Severe congenital neutropenia
• Disease Identifiers:
  MONDO ID: MONDO_0018542
  UMLS CUI: C1853118
  MedGen ID: 343974
  Orphanet ID: 42738

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CSF1R	TT7MRDV	Limited	Altered Expression	[1]
HAX1	TT21BYA	Limited	Genetic Variation	[2]
G6PC	TTBQMJ8	moderate	Genetic Variation	[3]
KAT6A	TT6O1J0	moderate	Genetic Variation	[4]
SLC37A4	TT1KPBZ	Strong	Genetic Variation	[5]
TCIRG1	TTVRN05	Strong	Genetic Variation	[6]
WAS	TTE8T73	Strong	Altered Expression	[7]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GATA2	OTBP2QQ2	Limited	Genetic Variation	[8]
CHD2	OTRKL6YC	moderate	Genetic Variation	[4]
GFI1	OT9HB9H8	Moderate	Autosomal dominant	[9]
HUWE1	OTFH6BJS	moderate	Genetic Variation	[4]
ARHGDIA	OTEXWJDO	Strong	Posttranslational Modification	[10]
ARHGDIB	OT9PD6CS	Strong	Posttranslational Modification	[10]
CDK2AP2	OTR99SJ8	Strong	Genetic Variation	[11]
CLPB	OT1I0IBK	Strong	Biomarker	[12]
DDX41	OT6KEIHP	Strong	Biomarker	[13]
HCLS1	OTX7WGYN	Strong	Genetic Variation	[14]
HOXB8	OTKHOD17	Strong	Genetic Variation	[15]
JAGN1	OTHBA8GT	Strong	Biomarker	[16]
LAMTOR2	OTHEDISB	Strong	Genetic Variation	[11]
LEF1	OTWS5I5H	Strong	Altered Expression	[17]
RPP14	OT4OYFSK	Strong	Genetic Variation	[11]
RPS19	OTBKGP48	Strong	Biomarker	[18]
SF3B6	OTPRKS6S	Strong	Genetic Variation	[11]
SRI	OT4R3EAC	Strong	Biomarker	[19]
STAT5B	OTZVPEBT	Strong	Altered Expression	[20]

References

• [1] Defective G-CSFR signaling pathways in congenital neutropenia.Hematol Oncol Clin North Am. 2013 Feb;27(1):75-88, viii. doi: 10.1016/j.hoc.2012.11.001. Epub 2012 Nov 27.
• [2] Coexistence of Gaucher Disease and severe congenital neutropenia.Blood Cells Mol Dis. 2019 May;76:1-6. doi: 10.1016/j.bcmd.2018.07.001. Epub 2018 Aug 10.
• [3] Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation.J Crohns Colitis. 2020 Jan 1;14(1):142-147. doi: 10.1093/ecco-jcc/jjz112.
• [4] Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability.Am J Med Genet A. 2017 Jan;173(1):62-71. doi: 10.1002/ajmg.a.37969. Epub 2016 Sep 12.
• [5] Congenital neutropenia.Hematology Am Soc Hematol Educ Program. 2009:344-50. doi: 10.1182/asheducation-2009.1.344.
• [6] Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project.Genet Epidemiol. 2016 Sep;40(6):470-4. doi: 10.1002/gepi.21976. Epub 2016 May 27.
• [7] Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive.J Clin Invest. 2018 Aug 31;128(9):4115-4131. doi: 10.1172/JCI64772. Epub 2018 Aug 20.
• [8] GATA2 deficiency.Curr Opin Allergy Clin Immunol. 2015 Feb;15(1):104-9. doi: 10.1097/ACI.0000000000000126.
• [9] Inflammatory reactions and severe neutropenia in mice lacking the transcriptional repressor Gfi1. Nat Genet. 2002 Mar;30(3):295-300. doi: 10.1038/ng831. Epub 2002 Jan 28.
• [10] Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia.Blood. 2000 May 1;95(9):2947-53.
• [11] Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia.Br J Haematol. 2009 Feb;144(4):459-67. doi: 10.1111/j.1365-2141.2008.07425.x. Epub 2008 Dec 10.
• [12] CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.Am J Hum Genet. 2015 Feb 5;96(2):245-57. doi: 10.1016/j.ajhg.2014.12.013. Epub 2015 Jan 15.
• [13] Germline Genetic Predisposition to Hematologic Malignancy.J Clin Oncol. 2017 Mar 20;35(9):1018-1028. doi: 10.1200/JCO.2016.70.8644. Epub 2017 Feb 13.
• [14] In vitro study of HAX1 gene therapy by retro viral transduction as a therapeutic target in severe congenital neutropenia.Eur Cytokine Netw. 2018 Nov 1;29(4):146-152. doi: 10.1684/ecn.2018.0419.
• [15] Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo.PLoS One. 2016 Dec 12;11(12):e0168055. doi: 10.1371/journal.pone.0168055. eCollection 2016.
• [16] Next-Generation Sequencing Reveals A JAGN1 Mutation in a Syndromic Child With Intermittent Neutropenia.J Pediatr Hematol Oncol. 2019 May;41(4):e266-e269. doi: 10.1097/MPH.0000000000001256.
• [17] Bortezomib inhibits STAT5-dependent degradation of LEF-1, inducing granulocytic differentiation in congenital neutropenia CD34(+) cells.Blood. 2014 Apr 17;123(16):2550-61. doi: 10.1182/blood-2012-09-456889. Epub 2014 Jan 6.
• [18] Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation.Clin Genet. 2011 May;79(5):448-58. doi: 10.1111/j.1399-0004.2010.01468.x.
• [19] Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation.Ann Hematol. 2011 Feb;90(2):151-8. doi: 10.1007/s00277-010-1056-4. Epub 2010 Aug 28.
• [20] A Truncated Granulocyte Colony-stimulating Factor Receptor (G-CSFR) Inhibits Apoptosis Induced by Neutrophil Elastase G185R Mutant: IMPLICATION FOR UNDERSTANDING CSF3R GENE MUTATIONS IN SEVERE CONGENITAL NEUTROPENIA.J Biol Chem. 2017 Feb 24;292(8):3496-3505. doi: 10.1074/jbc.M116.755157. Epub 2017 Jan 10.