Spastic paraplegia type 3A family (Spastic paraplegia 3A type -SPG3A-) Gene ATL1.
Paraplegia (or paraparesis) spastic type 3A (SPG3A) is one of spastic paraplegia known as heritable genetic damage. 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 the also affect the structure or function of the brain and peripheral nervous system.
The spastic paraplegia type 3A is a hereditary spastic paraplegia of pure type. In addition to muscle and regular feature spastic paraplegia weakness of hereditary rigidity, people with spastic paraplegia type 3A may also have amiotrofia in the lower extremities, decreased bladder control and scoliosis. Signs and symptoms of the disease usually appear in the first decade of life. The disease progresses very slowly, and some people may need help walking.
This process is due to mutations in the gene ATL1, located on the long arm of chromosome 14 (14q22.1). This gene encodes atlastina-1 protein, which is found throughout the body, particularly in the brain. In cells, this protein is found in the endoplasmic reticulum and Golgi apparatus, involved in the movement of proteins and cellular components within the cell. It is likely to play a role in protein transport of cellular components and forming the Golgi apparatus and the endoplasmic reticulum, each involved in axon growth. Although atlastina-1 protein is required for the formation and growth of axons, its precise role is unclear. Furthermore, it is likely that this protein plays a role in the normal functioning of multiple structures within neurons and the distribution of materials within these cells.
They have identified 60 mutations in the gene ATL1 causing spastic paraplegia 3A type. Most of these mutations change an amino acid in atlastina-1 protein. It is believed that these mutations lead to a deficiency of normal protein atlastin-1, disrupting the function of neurons, including distribution of substances within these cells. Furthermore, functional protein deficiency atlastin-1 may also limit the growth of axons. These problems can cause abnormal operation or death of neurons in the corticospinal tract. As a result, the neurons are unable to transmit nerve impulses, particularly to other neurons and muscles of the lower extremities. This altered nerve function causes the signs and symptoms of spastic paraplegia type 3A.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. In some cases, an affected person inherits the mutation from an affected parent. Other cases result from new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with spastic paraplegia 3A type, by complete PCR amplification of exons ATL1 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).