Parkinson recessive juvenile (Juvenile form of Parkinson 's disease) - Gen PARK2.
Parkinson's disease is a progressive disorder of the nervous system. This disease affects various brain regions, especially the substantia nigra, which controls balance and movement. Often the first symptom of the disease is the tremor of a limb, especially when the body is at rest. Overall, the shaking starts on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet and face. Other characteristic symptoms of Parkinson's disease include rigidity , or stiffness of the limbs and trunk, bradykinesia, akinesia and postural instability. These symptoms slowly worsen over time.
Parkinson's disease can also affect emotions and knowledge. Some affected individuals develop psychiatric illnesses such as depression and visual hallucinations. People with Parkinson 's disease also have an increased risk of developing dementia. In the recessive juvenile Parkinson's disease occurs before 20 years of age.
Most cases of Parkinson's disease are probably due to a complex interaction of environmental and genetic factors. The recessive juvenile Parkinson's due to changes in the PARK2 gene, located on the long arm of chromosome 6 (6q25.2-q27). This gene encodes a protein called parkin. This protein plays a role in cellular processes that degrade proteins that are not required by marking damaged proteins and excess ubiquitin molecules. Ubiquitin serves as a signal to move the proteins that are necessary to proteasomes, where proteins are degraded. The ubiquitin-proteasome system acts as quality control of the cell by the arrangement of damaged proteins, and excess protein deformed. This system also regulates the availability of proteins that are involved in several critical cellular activities such as cell division and growth. Because of their activity in the ubiquitin-proteasome system, parkin belongs to a group of proteins called ubiquitin E3 ligases.
In addition, parkin seems to be involved in maintaining mitochondria. However, little is known about its role in mitochondrial function. In this sense, it is likely that parkin contribute to trigger the destruction of the mitochondria are not working properly. It is believed that parkin can act as a tumor suppressor protein and may regulate the supply and synaptic vesicle release from nerve cells.
There are more than 200 mutations in the gene PARK2 result in Parkinson's disease. Mutations in this gene are associated with the juvenile form of Parkinson's disease, manifested before age 20, and some cases of the most common, late - onset which starts after 50 years. Some PARK2 genetic mutations lead to an abnormally small parkin protein is nonfunctional and rapidly decomposes within the cells. Other mutations inserted, deleted or changed nucleotides in PARK2 gene, resulting in a defective version of parkin protein or inhibiting encoding this protein. Usually, all mutations in the gene PARK2 associated with Parkinson's disease leading to a loss of activity of parkin. Although it is unclear how genetic mutations result in PARK2 disease, it is likely that the loss of activity of parkin disturb the ubiquitin-proteasome system, causing an accumulation of proteins that are not necessary. An accumulation of these proteins could disrupt normal cellular activities such as feeding and outlet of synaptic vesicles, especially those containing dopamine. Because parkin is abundant in the brain, its loss could lead to failure or death of nerve cells, including those that produce dopamine. The loss of dopamine - producing nerve cells is a characteristic feature of Parkinson's disease. Mutations in the gene may also disrupt PARK2 regulation of mitochondria. It is believed that mitochondrial dysfunction in dopamine - producing nerve cells can play an important role in the cause of the signs and symptoms of Parkinson's disease.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with recessive juvenile parkinsonism, by complete PCR amplification of the exons of the gene PARK2, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).