Paraplegia familial spastic type 2 (Spastic paraplegia type 2) - Gen PLP1.  

The spastic paraplegia type 2 is part of a group of genetic alterations known as hereditary spastic paraplegia. These changes are characterized by spasticity and development of paraplegia. Hereditary spastic paraplegia the are divided into two types: pure and complex. Pure types involving the lower extremities. Complex types involving the lower extremities and may affect the upper extremities to a lesser degree. Spastic paraplegia complex also affect the structure or function of the brain and peripheral nervous system consists of the nerves that connect the brain and spinal cord to muscles and sensory cells that detect sensation like touch, pain, heat , and sound. The spastic paraplegia type 2 can occur in both pure form and in the complex.

People with the pure form of the disease have spasticity in the lower extremities, usually without additional features. People with complex form have the limb spasticity, also being possible ataxia, nystagmus, mild mental retardation, tremors and atrophy of the optic nerves. Symptoms usually appear between the ages of 1 and 5 years. Generally, affected individuals are able to walk and have a normal life expectancy.

This process is due to mutations in the PLP1, located on the long arm of chromosome X (Xq22). This gene encodes the proteolipid protein 1 and protein isoform called DM20. Proteolipid protein 1 and protein DM20 are mainly found in the brain and spinal cord and are the major proteins found in myelin that protects nerve fibers, and which promotes rapid transmission of nerve impulses. The DM20 protein is mainly involved in the formation of myelin before birth, while the proteolipid protein 1 is the predominant protein after birth ..

They have identified more than 10 mutations in the PLP1 causing spastic paraplegia type 2. Most mutations change an amino acid in an area not critical proteolipid protein 1. Some of these mutations disrupt the production of the proteolipid protein 1 but do not interfere with the production of its isoform DM20. When proteolipid protein 1 and DM20 missing demyelination which can impair the function of the nervous system occurs, leading to the signs and symptoms of the spastic paraplegia type 2.

This disease is inherited as a recessive X - linked pattern A condition is considered X - linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males, an altered copy of the gene in each cell is sufficient to cause disease. In women, an altered copy of the gene in each cell usually leads to less severe symptoms or may cause no symptoms at all. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In the X - linked recessive inheritance, a woman with an altered copy of the gene in each cell is called a carrier. She can pass the gene, but generally have no signs and symptoms of the disease. However, some women who carry a mutation in the PLP1 gene may have muscle stiffness and decreased intellectual function. Women with a mutation in the gene have a higher risk of developing dementia.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with spastic paraplegia type 2 by PCR amplification of complete exons PLP1 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).