Diagnostics in GSS

How to find out if you are sick (or prepared to) Gerstmann Straussler Scheinker's disease.

As we have written, we are dealing with a fatal disease, autosomal dominant with high penetrance and which can affect from about 30 to 60 years, with a maximum incidence between 40 and 55 years. If we are faced with a P102L mutation, the most widespread in the world, generally the first symptoms are pain in the legs and back, difficulty in walking etc. To have an early diagnosis it is necessary to undergo a DNA TEST, which generally takes place via Western Blot. The patient only has to undergo a blood sample.
The western blot or immunoblot is a biochemical technique that allows to identify a specific protein in a mixture of proteins, through the recognition by specific antibodies; in general, to facilitate recognition, the protein blend is first separated based on their size (or molecular weight) using a polyacrylamide gel (but there are variations such as dot blot or slot blot, in which the protein blend is not separated based on size, but relying on antigen / antibody selectivity); subsequently the proteins are transferred on a support, which is commonly a nitrocellulose membrane, and then the actual recognition of the protein is carried out through the use of a specific antibody.

Recently, techniques have been developed that allow antigen / antibody recognition directly in the gel matrix, thus avoiding membrane transfer. This technique is used when the sample is composed of a mixture of many proteins such that with a standard color (Coomassie blue or silver nitrate) it would not be possible to distinguish them from each other, or when, despite having very distinct bands (discrete), the protein of interest is too low to be visualized with other techniques. In fact, the western has three steps in which the amplification of the signal takes place, which makes even tenths of a pico mole (10-12mol) of protein visible. Sample proteins are also separated using gel electrophoresis. In this case, protein separation can occur by isoelectric point (pI), molecular weight, electric charge, or a combination of these factors.
The nature of the separation depends on the handling of the sample and the nature of the gel. This way is the most used to identify a protein. The most common type of gel electrophoresis employs polyacrylamide gels (Polyacrylamide Gel Electrophoresis) and sodium lauryl sulfate (SDS) loaded pads. SDS-PAGE (SDS polyacrylamide gel electrophoresis) maintains polypeptides in a denatured state when treated with strong reducing agents to remove secondary and tertiary structures (e.g. disulfide [SS] and mercaptan groups [SH and SH]) and allow for the separation of proteins based on their molecular weight. The sampled proteins bind the SDS which gives them a negative charge and thus move towards the positive electrode through the gel meshes. Smaller proteins migrate faster through this mesh, and proteins are separated by size (measured in kilo Dalton, kDa).

The concentration of acrylamide determines the resolution of the gel - the higher the concentration, the better the resolution of low molecular weight proteins. Proteins only travel in one dimension along the gel for several blots. Samples are loaded into wells in the gel. A strip is usually reserved for a marker or scale, a commercial blend of proteins of defined molecular weight, typically colored to form visible colored bands. When electrical voltage is applied along the gel, proteins migrate through it at different rates, depending on their size. These different speeds of advancement (electrophoretic mobility) allow the separation into bands within each lane.

Below is an image of a Western blot analyzer:

The result will tell us if there is positivity to the gene PRPN

Through a neurologist or a neuropathologist, we will be able to find out if we are ill with Gerstmann Straussler Scheinker. One may also be just predisposed, albeit asymptomatic. This means that the disease will develop. It is not possible to know when or how but it will develop.