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 | 202700 162800 | 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 |
 | 301000 | Severe permanent Maturation arrest | Monocytopenia | X Linked | Xp11.4-p11.21 | WAS | Cytoskeleton homeostasis | |
 | WHIM [99] | 193670 | Severe permanent No maturation arrest Myelokathexis | Lymphopenia Thrombocytopenia | Dominant | 2q21 | CXCR4 | Chemokine receptor (CXCL12) |
Congenital neutropenia with extra hematopoietic manifestations | 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 Uropathy | 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 |
 | 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 |
 | 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 |