Spastic paraplegia type 15 family (Spastic paraplegia type 15) - Gen ZFYVE26.
The spastic paraplegia type 15 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. In addition to the muscles and brain, spastic paraplegia type 15 affects the peripheral nervous system.
The disease becomes evident in childhood or adolescence with the development of hypotonia, difficulty walking, or intellectual disabilities. In almost all those affected, the union between the two brain, right and left hemispheres, is abnormally thin, becoming thinner over time. Often atrophy of nerve cells in several parts of the brain, including the cerebral cortex, which controls thought and emotions, and the cerebellum, which coordinates movement occurs. Affected individuals may have sensory neuropathy, motor neuropathy, hyperreflexia of the lower limbs, muscular atrophy or decreased bladder control. Rarely, the disease is associated with parkinsonism. People with the disease may have an eye condition called pigmentary maculopathy that often impairs vision. This alteration is due to tissue degeneration in the macula, which is responsible for sharp central vision. Most people with spastic paraplegia type 15 develop over time a decrease in intellectual capacity and an increase in muscle weakness and nervous disorders. As the disease progresses, many people require assistance to walk or a wheelchair into adulthood.
This process is due to mutations in the gene ZFYVE26, located on the long arm of chromosome 14 (14q24.1). This gene encodes the protein espastizina, found in most tissues. This protein is important in a process called autophagy, in which parts of worn cells and proteins that are not needed are recycled within cells. More specifically, the protein is involved in the formation and maturation of Autophagosomes or autophagic vacuoles. The protein also plays a role in the process of cytokinesis.
There are more than 30 mutations in the gene ZFYVE26 causing spastic paraplegia type 15. Mutations in the gene, resulting in a shortened protein espastizina rapidly decomposes. As a result, nonfunctional Autophagosomes occur, thereby autophagy and recycling of materials within cells decreases can not occur. An inability to break down unneeded materials, and subsequent accumulation of these materials in cells, leading to dysfunction and often death cell. Loss of cells in the brain and other parts of the body is responsible for many of the characteristics associated with the 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 spastic paraplegia type 15, by complete PCR amplification of exons ZFYVE26 gene, 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).