Characteristics of the test: (includes 1 gene)
NF1 (OMIM #613113)

Basic characteristics of the clinical phenotype:
Neurofibromatosis is a genetic disease that leads to the development of tumors affecting the entire nervous system (brain and spinal cord, nerves), characteristic "coffee with milk" skin pigmentation, forming a multiple, mostly benign fibromatous skin tumors - the so-called neurofibromas. It is most often diagnosed in childhood or early adulthood. Symptoms are often mild, but complications of the disease can lead to hearing loss, mental retardation, problems with the cardiovascular system, loss of vision, and severe pain.

Neurofibromatosis (benign) or the so-called von Recklinghausen's disease comes in two separate, genetically and clinically different forms - type 1 and type 2. Neurofibromatosis type 1 (NF1) is an autosomal dominant disease presenting with the characteristic "coffee with milk" skin pigmentation, multiple tumors in the central and peripheral nervous system system, cerebrovascular changes and damage to internal organs. The estimated incidence of NF1 is 1 in 2,500-3,300 live births regardless of race, sex, or ethnicity, with about half of cases being caused by new (de novo) spontaneous mutations.

These mutations may result from germline mosaicism in apparently unaffected parents. The disease is characterized by a wide variability of the clinic - from mild asymptomatic forms to very severe manifestations of the clinical picture and a high risk of malignant diseases threatening the patient's life.
NF1 arises as a result of mutations leading to loss of function of the NF1 gene located on the long arm of chromosome 17 (17q11.2). The NF1 gene encodes a protein called neurofibromin, which acts as a tumor suppressor gene. Neurofibromin is associated with tropomyosin fibrils of the cytoskeleton in various tissues.

The endoplasmic reticulum of neurons is the richest in neurofibromin. Mutations in NF1 disrupt the structure of neurofibromin and inactivate it, greatly accelerating the proliferation of certain cells and pushing them toward tumorigenesis. Over 100 different germline mutations have been described in this gene, including deletions of various sizes, insertions, single nucleotide base substitutions of the transition or transversion type, splicing errors, translocations, etc.

Indications  for Referral / Clinical Significance:
For the study of large deletions/duplications, rearrangements in the NF1 gene, patients with a diagnosis of Neurofibromatosis type 1, examined with Test No. 35 and without detected mutations in the NF1 gene or close relatives of patients in whom an aberration in the NF1 gene was detected, are referred.

Interpretаtion of results:
· Detection of deletions/duplications/rearrangements in the NF1 gene allows the diagnosis of Neurofibromatosis type 1.
· The genetic counselor will interpret and answer all questions about your result.

Method: MLPA (Multiplex Ligation Dependent Probe Amplification)
MLPA is a semi-quantitative method for determining DNA copy number. The methodology is used to detect intragenic or whole-gene deletions or duplications. Large deletion/duplication search analysis was performed using the MRC-Holland (Amsterdam, Holland) SALSA MLPA P081 NF1 and SALSA MLPA P082 NF1 set.

Sensitivity of the method: 90%

What does the test involve?

· DNA isolation and sample storage.

· MLPA to detect large deletions/duplications affecting the NF1 gene.

· Forming a written result of the genetic test.

· Diagnostic interpretation of results and genetic counseling.


Biological material: Venous blood or DNA
For more information, please read the "Biological material requirements and shipping information" carefully.