Congenital Neutropenia Precision Panel
Neutropenia is a dangerous and potentially fatal condition that exposes patients to recurrent infections. Primary causes constitute a small portion of the whole and are mostly unknown.
Overview
Neutropenia is a dangerous and potentially fatal condition that exposes patients to recurrent infections. Primary causes constitute a small portion of the whole and are mostly unknown. Congenital neutropenia is a primary immunodeficiency disorder associated with recurrent bacterial infections, auto-inflammatory and auto-immune phenomena, hematologic malignancy and neuro-psychiatric manifestations. It results from impaired maturation of neutrophil granulocytes and is associated with a variety of syndromic diseases including: oculocutaneous albinism, metabolic diseases and bone marrow failure syndromes. Congenital neutropenia is a genetically heterogeneous group of related disorders. It demonstrates several modes of inheritance, including autosomal recessive, autosomal dominant, sporadic and X-linked forms.
The Igenomix Congenital Neutropenia Precision Panel can be as a tool for an accurate and directed diagnosis as well as differential diagnosis of recurrent bacterial infections ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
- The Igenomix Congenital Neutropenia Precision Panel is used for patients with a clinical diagnosis or suspicion with or without the following symptoms:
- Oral ulcers
- Gingivitis
- Pharyngitis
- Sinusitis, otitis media
- Lymphadenopathy, lymphadenitis
- Bronchitis, pneumonia
- Cellulitis
- Cutaneous abscess
- Abscesses
- Bacteremia and/or septicemia
- Urinary tract infection
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment involving a multidisciplinary team focusing on preventive care of infections and other complications, symptomatic medical care for neurologic symptoms alongside early surveillance for cancer detection.
- Risk assessment of asymptomatic family members according to the mode of inheritance via genetic counselling and explanation of the multisystem nature of the disease.
- Improvement of delineation of genotype-phenotype correlation.
Genes & Diseases
See all genes and diseases
GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
AK2 | Reticular | AR | 100 | 21 of 21 |
AP3B1 | Hermansky- | AR | 100 | 34 of 35 |
CD40LG | X-linked Immuno- | X,XR,G | 100 | – |
CLPB | 3-a Methy | AR | 96 | 26 of 26 |
CSF3R | Severe | AR | 99.99 | 19 of 19 |
CXCR2 | Severe | – | 99.94 | 1 of 1 |
CXCR4 | Whim | AD | 100 | 19 of 19 |
DNAJC21 | Bone Marrow | AR | 99.83 | 12 of 12 |
EFL1 | Shwachman- | AR | 99.94 | – |
EIF2AK3 | Multiple | AR | 99.3 | 89 of 89 |
ELANE | Cyclic | AD | 100 | 227 of 227 |
G6PC3 | Severe | AR | 100 | 45 of 45 |
GATA1 | X-linked | X,XR,G | 99.93 | – |
GATA2 | Dendritic Cell, | AD | 100 | 137 of 142 |
GFI1 | Nonimmune | AD | 98.77 | 4 of 4 |
HAX1 | Severe | AR | 100 | 22 of 23 |
HYOU1 | Immuno- | AR | 99.94 | 2 of 2 |
JAGN1 | Severe | AR | 99.95 | 10 of 10 |
LAMTOR2 | Immuno- | AR | 100 | 1 of 1 |
LYST | Chediak- | AR | 99.98 | 117 of 117 |
MRTFA | Immuno- | AR | 99.8 | – |
RAB27A | Griscelli | AR | 100 | 54 of 55 |
RAC2 | Immuno- | AD,AR | 100 | 5 of 5 |
RMRP | Anauxetic | AR | – | – |
RUNX1 | Acute Myeloid | AD | 99.83 | 90 of 90 |
SBDS | Aplastic | AR | 100 | 77 of 79 |
SLC37A4 | Glycogen | AR | 99.97 | 112 of 112 |
SMARCD2 | Specific | AR | 91.58 | 1 of 1 |
SRP54 | Severe | AD,AR | 99.95 | 8 of 8 |
STK4 | T-Cell | AR | 99.88 | 10 of 10 |
TAZ | Barth | X,XR,G | 100 | – |
TCIRG1 | Autosomal | AR | 100 | 140 of 146 |
TCN2 | Transcobalamin | AR | 100 | 25 of 27 |
TP53 | Bone Marrow | AD,MU,P | 98.92 | 557 of 563 |
USB1 | Poikiloderma | AR | 100 | 24 of 24 |
VPS13B | Cohen | AR | 99.98 | 182 of 190 |
VPS45 | Severe | AR | 100 | 4 of 4 |
WAS | Severe | X,XR,G | 100 | – |
WDR1 | Periodic | AR | 100 | 9 of 9 |
WIPF1 | Wiskott-Aldrich | AR | 99.79 | 3 of 3 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial
** HGMD: Number of clinically relevant mutations according to HGMD
References
Spoor, J., Farajifard, H., & Rezaei, N. (2019). Congenital neutropenia and primary immunodeficiency diseases. Critical reviews in oncology/hematology, 133, 149–162. https://doi.org/10.1016/j.critrevonc.2018.10.003
Donadieu, J., Beaupain, B., Fenneteau, O., & Bellanné-Chantelot, C. (2017). Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. British journal of haematology, 179(4), 557–574. https://doi.org/10.1111/bjh.14887
Donadieu, J., Fenneteau, O., Beaupain, B., Mahlaoui, N., & Chantelot, C. B. (2011). Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet journal of rare diseases, 6, 26. https://doi.org/10.1186/1750-1172-6-26
Klein, C., Grudzien, M., Appaswamy, G., Germeshausen, M., Sandrock, I., & Schäffer, A. et al. (2006). HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nature Genetics, 39(1), 86-92. doi: 10.1038/ng1940
Klein, C. (2009). Congenital neutropenia. Hematology, 2009(1), 344-350. doi: 10.1182/asheducation-2009.1.344
Ward, A., & Dale, D. (2009). Genetic and molecular diagnosis of severe congenital neutropenia. Current Opinion In Hematology, 16(1), 9-13. doi: 10.1097/moh.0b013e32831952de
Boztug, K., & Klein, C. (2013). Genetics and pathophysiology of severe congenital neutropenia syndromes unrelated to neutrophil elastase. Hematology/oncology clinics of North America, 27(1), 43–vii. https://doi.org/10.1016/j.hoc.2012.11.004
