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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

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

 

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

Myelokathexis

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

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

 

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