Juvenile primary lateral sclerosis (Juvenile primary lateral sclerosis) - Gen ALS2.
Juvenile primary lateral sclerosis is a rare disease characterized by progressive spasticity of the muscles of the arms, legs and face. The characteristics of this disorder are caused by damage to motor neurons. Symptoms of juvenile primary lateral sclerosis begin in early childhood and progress slowly over many years. Early symptoms include clumsiness, muscle weakness and spasticity in the legs and difficulty with balance. As symptoms progress, spasticity spreads to the arms and hands and individuals manifest difficulty speaking, difficulty swallowing , and inability to walk.
This process is due to mutations in the ALS2 gene, located on the long arm of chromosome 2 (2q33.1). This gene encodes the protein alsin. Alsina occurs in a wide range of tissues, with higher amounts in the brain. This protein is particularly abundant in motor neurons. Although alsina seems to have many functions, only a few are known. This active protein GTPases that convert GTP to GDP. GTPases play an important role in cell division, differentiation and apoptosis. In addition, it is likely that alsina play a role in endocytosis and the development of axons and dendrites.
They have identified 3 mutations in the gene ALS2 in people with juvenile primary lateral sclerosis. Two of the mutations identified deleted nucleotides, and a mutation replaces a nucleotide by an incorrect nucleotide. These mutations alter the protein coding resulting in an unstable protein alsina and rapidly decomposes by the cell, or can not function properly. Although it is unclear how loss of protein Alsina functional causes juvenile primary lateral sclerosis, loss of alsina can lead to an interruption of the movement of molecules within cells or impair the development of axons and dendrites. It is likely that motor neurons and their long axons may be particularly vulnerable to changes in cell development. This compromises the function of motor neurons and eventually these nerve cells die, leading to the signs and symptoms of juvenile primary lateral sclerosis.
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 juvenile primary lateral sclerosis, by complete PCR amplification of exons ALS2 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).