©istock.com/Andrea Obzerova
Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessNeutropenia, congenital; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Neutropenia containing 10 guideline-curated genes and altogether >50 curated genes in the context of the suspected diagnosis

ID
NP9448
Number of genes
33 Accredited laboratory test
Examined sequence length
17,1 kb (Core-/Core-canditate-Genes)
64,2 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GHeredity
CSF3R2511AR
CXCR41059AD
DNAJC212049AR
ELANE804AD
G6PC31041AR
GATA11242XLR
GFI11269AD
HAX1840AR
RMRP300AR
SRP541534AD
TCN21284AR
VPS451617AR
WAS1509XLR
ACD1647AD, AR
ACKR11017AR
AK2675AR
CTC13654AR
DKC11545XLR
EFL13382AR
G6PC11074AR
LYST11406AR
MLPH1719AR
MYO5A5568AR
NHP2273AR
NOP10195AR
PARN1920AD, AR
RAB27A666AR
RTEL13732AD, AR
SLC37A41291AR
TAFAZZIN879XLR
TERT3399AR
TINF21356AD
WRAP531647AR

Informations about the disease

Clinical Comment

Severe congenital neutropenia renders affected individuals susceptible to recurrent infections. Neutropenia can occur in the perinatal period or lateron. The recurrent infections begin in infancy and include sinusitis, pulmonary and hepatic affections, which may be accompanied by fever, gingivitis and skin inflammation. Nearly half of these patients have osteopenia and may develop osteoporosis. Bone involvement may begin in infancy or as late as adulthood. Approximately 20% of these patients develop certain blood malignancies in adolescence, particularly myelodysplastic syndrome or leukemia. A few affected individuals have additional health problems such as seizures, developmental delays or cardiac and genital abnormalities. Congenital neutropenia can be caused by mutations in many different genes. These genes play a role in the maturation and function of neutrophils, which secrete e.g. immune molecules. The life span of neutrophils is shortened, and their function is impaired or the physiological maturation is impaired. About half of all cases of severe congenital neutropenia are caused by mutations in the ELANE gene, another 10% by mutations in the HAX1 gene. Mutations in other genes are each responsible for only a small percentage of all cases. In about one third of these patients, the cause remains unknown. Most cases of severe congenital neutropenia are classified as sporadic. When congenital neutropenia is caused by mutations in the ELANE gene, it is inherited in an autosomal dominant manner (as it is for mutations in other genes). If the disease is caused by alterations in the HAX1 gene, it is inherited in an autosomal recessive manner (like in other cases). Less commonly, severe congenital neutropenia is inherited in an X-linked recessive manner. A negative molecular genetic result by no means excludes the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1533/

https://www.ncbi.nlm.nih.gov/books/NBK571103/

https://www.ncbi.nlm.nih.gov/books/NBK1756/

https://www.ncbi.nlm.nih.gov/books/NBK285321/

https://www.ncbi.nlm.nih.gov/books/NBK247162/

 

Synonyms
  • Allelic: 3-methylglutaconic aciduria, type VIIB, AR (CLPB)
  • Allelic: Aplastic anemia, susceptibility to (SBDS)
  • Allelic: Blood group, Duffy system (AKCR1)
  • Allelic: Cartilage-hair hypoplasia (RMRP)
  • Allelic: Leukemia, acute myeloid (TERT)
  • Allelic: Malaria, vivax, protection against (AKCR1)
  • Allelic: Melanoma, cutaneous malignant, 9 (TERT)
  • Allelic: Metaphyseal dysplasia without hypotrichosis (RMRP)
  • Allelic: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1 (TERT)
  • Allelic: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 (RTEL1)
  • Allelic: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4 (PARN)
  • Allelic: Revesz syndrome (TINF2)
  • Allelic: Thrombocytopenia with beta-thalassemia, XL (GATA1)
  • Allelic: Thrombocytopenia, XL (WAS)
  • Allelic: Thrombocytopenia, XL, intermittent (WAS)
  • Allelic: Thrombocytopenia, XL, with/-out dyserythropoietic anemia (GATA1)
  • Allelic: Wiskott-Aldrich syndrome (WAS)
  • Anauxetic dysplasia 1 (RMRP)
  • Anemia, XL, with/-out neutropenia +/- platelet abnormalities (GATA1)
  • Ataxia-pancytopenia syndrome (SAMD9L)
  • BM failure syndrome, AR [panelapp] (NAF1)
  • Barth syndrome [3-methylglutaconic aciduria type II] (TAFAZZIN)
  • Bone marrow failure syndrome 3 (DNAJC21)
  • Bone marrow failure syndrome 5 (TP53)
  • Cerebroretinal microangiopathy with calcifications + cysts (CTC1)
  • Cerebroretinal microangiopathy with calcifications + cysts 2 (STN1)
  • Chediak-Higashi syndrome (LYST)
  • Cohen syndrome (VPS13B)
  • Congenital disorder of glycosylation, type IIw (SLC37A4)
  • Dursun syndrome (G6PC3)
  • Dyskeratosis congenita [panelapp] (NAF1)
  • Dyskeratosis congenita, AD (TINF2)
  • Dyskeratosis congenita, AD 2 (TERT)
  • Dyskeratosis congenita, AD 4 (RTEL1)
  • Dyskeratosis congenita, AD 6 (ACD)
  • Dyskeratosis congenita, AR 1 (NOP10)
  • Dyskeratosis congenita, AR 2 (NHP2)
  • Dyskeratosis congenita, AR 3 (WRAP53)
  • Dyskeratosis congenita, AR 4 (TERT)
  • Dyskeratosis congenita, AR 5 (RTEL1)
  • Dyskeratosis congenita, AR 6 (PARN)
  • Dyskeratosis congenita, AR 7 (ACD)
  • Dyskeratosis congenita, XL (DKC1)
  • Emberger syndrome (GATA2)
  • Glycogen storage disease Ia (G6PC1)
  • Glycogen storage disease Ib (SLC37A4)
  • Glycogen storage disease Ic (SLC37A4)
  • Griscelli syndrome, type 1 (MYO5A)
  • Griscelli syndrome, type 2 (RAB27A)
  • Griscelli syndrome, type 3 (MLPH)
  • Hermansky-Pudlak syndrome 2 (AP3B1)
  • Immunodeficiency 21 (GATA2)
  • Immunodeficiency due to defect in MAPBP-interacting protein (LAMTOR2)
  • Immunodeficiency, XL, with hyper-IgM (CD40LG)
  • MIRAGE s.: Myelodysplasia, Infection, Restric. growth, Adrenal hypopl., Genital-/Enteropathy (SAMD9)
  • Monosomy 7 myelodysplasia + leukemia syndrome 1 (SAMD9L)
  • Monosomy 7 myelodysplasia + leukemia syndrome 2 (SAMD9)
  • Myelokathexis, isolated (CXCR4)
  • Neutropenia, alloimmune neonatal [panelapp] (FCGR3B)
  • Neutropenia, cyclic (ELANE)
  • Neutropenia, nonimmune chronic idiopathic, of adults (GFI1)
  • Neutropenia, severe congenital 1, AD (ELANE)
  • Neutropenia, severe congenital 2, AD (GFI1)
  • Neutropenia, severe congenital 3, AR (HAX1)
  • Neutropenia, severe congenital 4, AR (G6PC3)
  • Neutropenia, severe congenital 5, AR (VPS45)
  • Neutropenia, severe congenital 6, AR (JAGN1)
  • Neutropenia, severe congenital 7, AR (CSF3R)
  • Neutropenia, severe congenital 8, AD (SRP54)
  • Neutropenia, severe congenital 9, AD (CLPB)
  • Neutropenia, severe congenital XL (WAS)
  • Osteopetrosis, AR 1 (TCIRG1)
  • Osteopetrosis, infantile malignant (TCIRG1)
  • Poikiloderma with neutropenia (USB1)
  • Pyogenic sterile arthritis, pyoderma gangrenosum, acne (PSTPIP1)
  • Reticular dysgenesis (AK2)
  • Shwachman-Diamond syndrome (SBDS)
  • Shwachman-Diamond syndrome 2 (EFL1)
  • T-cell immunodeficiency, recurrent infections, autoimmunity, cardiac malformations (STK4)
  • Transcobalamin II deficiency (TCN2)
  • WHIM [Warts, Hypogammaglobulinemia, Infections, Myelokathexis] syndrome 1 (CXCR4)
  • White blood cell count QTL (AKCR1)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code
D70.6

Bioinformatics and clinical interpretation

No text defined