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Do you know which gene mutation causes severe congenital neutropenia?
Severe congenital neutropenia (SCN) is a group of rare diseases that mainly affects the hematopoietic process of the bone marrow, resulting in congenital neutrophil deficiency. The disease usually manifests in infancy and is associated with life-threatening bacterial infections. Common symptoms include severe purulent infection, which can be particularly fatal in young children.
The most common inheritance pattern of SCN is autosomal dominant inheritance, mainly caused by mutations in the ELANE gene. This gene codes for neutrophil elastase.
Many patients with SCN may be diagnosed with detected ELANE mutations and result in severe neutropenia. The condition was first described by Swedish physician Rolf Kostmann in 1956 and came to be known as Kostmann's disease, a subtype of SCN.
Types of genetic mutations
There are many different genetic subtypes of SCN. SCN1 is the most common form, accounting for 60% to 80% of all cases. Other forms include SCN2 to SCN5, each of which is associated with different genetic mutations:
SCN1: Autosomal dominant, related to ELANE gene mutation.SCN2: Autosomal dominant, related to GFI1 gene mutation.SCN3: Autosomal recessive, related to HAX1 gene mutations, about one-third of patients will develop neurological-related changes.SCN4: Autosomal recessive, related to G6PC3 gene mutation, may be accompanied by cardiac structural abnormalities.SCN5: Autosomal recessive, related to VPS45 gene mutations, usually insensitive to proliferation factor treatment.
In addition, mutations in the WASP gene on the X chromosome can also cause X-linked SCN, and other genes such as SBDS may also be involved in this disorder.
Pathophysiology
Various genetic mutations that cause SCN lead to premature apoptosis of precursor cells in the bone marrow, often terminating development at the early blue cell stage. This significantly reduces the production of neutrophils, thereby increasing the risk of infection. . At the same time, abnormal gene expression in some patients may also lead to genomic instability.
Diagnostic methods
Diagnosis of SCN usually involves a detailed clinical examination, blood tests, and genetic testing. Patients often develop repeated severe infections due to low neutrophil counts. Initial testing includes a complete blood count (CBC) to assess the actual level of neutrophil count.
The diagnostic indicator of SCN is an absolute neutrophil count (ANC) consistently lower than 500/mm3, usually lower than 200/mm3.
In addition, a bone marrow biopsy is also a recommended procedure to evaluate the hematopoietic function of the bone marrow and rule out other possible blood disorders. Because SCN formation occurs in the early stages of hematopoiesis, only a limited number of mature cells are typically seen in the bone marrow.
Treatment Plan
Currently, the main treatment for SCN is regular injection of granular monocyte colony-stimulating factor (filgrastim), which can significantly increase the number of neutrophils and improve immune function. More than 90% of SCN patients respond well to this treatment, significantly extending their survival.
Although treatment improves survival rates, long-term complications that may occur in SCN patients, such as myelofibrosis and acute myeloid leukemia, remain a concern.
In summary, identification of genetic mutations is crucial for the treatment and management of SCN. This can not only help diagnose the disease but also provide targeted treatment options to improve the patient’s quality of life. However, do you think there are more unexplored areas in the study of disease-causing genes?
