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Table 1 Monogenic congenital neutropenia: Review of the known genes (2010)

From: Congenital neutropenia: diagnosis, molecular bases and patient management

Sub group of neutropenia Disease name/ref OMIM code Main hematological features Extra-hematopoeitic features Inheritance Gene localisation Gene (alias) Normal function of the gene
Congenital Neutropenia without extra hematopoeitic manifestations Severe congenital neutropenia/Cyclic neutropenia [8, 43] 202700
Severe and permanent
Maturation arrest
Intermittent/cyclic with variable bone marrow features
No Dominant 19q13.3 ELANE Protease activity
Antagonism with alpha 1 antitrypsin
  Severe congenital neutropenia Somatic mutation of CSF3R 202700 Permanent
Maturation arrest
Unresponsive to GCSF
No No genetic inheritence 1p35-p34.3 CSF3R transmembrane GCSF receptor/intracellular signalling
Congenital Neutropenia with innate or adaptive deficiency but no extrahematopoietic features Severe congenital neutropenia [88] 202700 Permanent/severe or mild
Sometimes maturation arrest
Internal ear (in mouse model) Lymphopenia Dominant 1p22 GFI1 Transcription factor
Regulation of oncoprotein
  Severe congenital neutropenia [89, 92] 301000 Severe permanent
Maturation arrest
Monocytopenia X Linked Xp11.4-p11.21 WAS Cytoskeleton homeostasis
  WHIM [99] 193670 Severe permanent
No maturation arrest
Lymphopenia Thrombocytopenia Dominant 2q21 CXCR4 Chemokine receptor (CXCL12)
Congenital neutropenia with extra hematopoietic manifestations Kostmann' disease [3, 4, 53, 232, 233] 202700 Maturation arrest Central nervous system: mental retardation/seizures Recessive 1q21.3 HAX1 Anti-apoptotic protein located in mitochondria and in the cytosol
  Shwachman-Bodian-Diamond disease [65] 260400 Mild neutropenia
Dysgranulopeosis mild dysmegacacyopoeisis
Exocrine Pancreas deficiency
Bone: metaphyseal dysplasia
Central nervous system: mental retardation Heart: cardiomyopathy
Recessive 7q11.22 SDBS Ribosomal protein Regulation of RNA expression
  Severe congenital neutropenia [10] 202700 Maturation arrest Skin -prominent superficial venous network
Heart: atrial defect
Recessive 17q21 G6PC3 Glucose 6 -phosphatase complex: Catalytic unit
  Barth disease [77] 302060 No maturation arrest Hypertrophy cardiomyopathy X Linked Xq28 TAZ (G4.5) Tafazzin: Phospholipid membrane homeostasis
  Hermansky- Pudlak syndrome type 2 [80] 608233 No maturation arrest Albinism Recessive 5q14.1 AP3B1 Cargo protein/ER traficking with ELANE interaction
  Neutropenia with AP14 mutation[78]   No maturation arrest Albinism Recessive 1q21 AP14 Lysosome packaging
  Poikilodermia type clericuzio[75, 76] 604173 No maturation arrest
Minor dysgranulopoetic features
Skin: poikilodermia Recessive 16q13 16ORF57 Not known
  Glycogen storage type Ib [234] 232220 No maturation arrest hypoglycemia, fasting hyperlactacidemia, and glycogen overload of the liver Recessive 11q23.3 SLC37A4 Glucose 6 -phosphatase complex: Trans ER Transporter
  Cohen syndrome[74] 216550 No maturation arrest psychomotor retardation, clumsiness, microcephaly, characteristic facial features, hypotonia and joint laxity, progressive retinochoroidal dystrophy, myopia Recessive 8q22-q23 VPS13B Sorting and transporting proteins in the ER
Diseases not usually assimilated to congenital neutropenia but including chronic neutropenia IRAK 4 deficiency [95] 606883 Permanent mild but severe infection
No maturation arrest
No Recessive 12q12 IRAK4 Mediators of Toll-like receptor signal transduction
  Dominant Charot Marie Tooth disease[137, 138] 602378 No maturation arrest Axonal neuropathy type Charcot Marie Tooth
Eyes: congenital cataract
Dominant 19p13.2-p12 DNM2 GTPases Regulation of the actin cytoskeleton
  Cartilage-hair hypoplasia [125] 250250 No maturation arrest Dwarfism metaphyseal dysplasia
Abnormal hair
Lymphopenia aganglionic megacolon
Recessive 9p21-p12 RMRP Endoribonuclease