Spinocerebellar ataxia type 36 (SCA36) (Spinocerebellar ataxia type 36) - Gen NOP56.

Spinocerebellar ataxia type 36 (SCA36) is a disease characterized by progressive movement problems usually begin in the middle adulthood. Initially, those affected manifest problems with coordination and balance. People usually present hyperreflexia, dysarthria and tongue twitches. Eventually, the tongue muscles atrophy which can cause dysphagia. As the disease progresses, individuals with SCA36 develop muscle atrophy in the legs, forearms and hands. Another common feature of SCA36 is the atrophy of motor neurons, which may contribute to muscle atrophy of the tongue and physical integrity in affected individuals. Some people with SCA36 have abnormalities of the eye muscles, which can lead to nystagmus, rapid eye movements, oculomotor apraxia and ptosis. In addition, affected individuals may have a sensorineural hearing loss.

Brain scans of people with SCA36 show progressive atrophy of various parts of the brain, especially in the cerebellum. Eventually, the loss of cells in the cerebellum leads to problems characteristic SCA36 movement. In affected individuals older, the frontal lobes of the brain atrophy may have caused the loss of executive function. Signs and symptoms of SCA36 usually start around 40 or 50 years of age, but can occur at any time during adulthood. People with SCA36 have a normal life expectancy and often have mobility over 15 to 20 years after being diagnosed.

This disease is due to mutations in the gene NOP56, located in short arm of chromosome 20 (20p13). This gene encodes a protein called nucleolar protein 56, which is primarily located in the nucleus of neurons, particularly in the cerebellum. This protein is a subunit of ribonucleoprotein complex, which is composed of proteins and RNA molecules. Ribonucleoprotein complex is needed to form ribosomes, the genetic instructions that process the cell to encode proteins.

Gene mutations causing SCA36 NOP56 involve a chain of six nucleotides located in an area of the intron-1 gene. This hexanucleotidica chain (GGCCTG) is normally represented several times in a sequence. In healthy individuals, the hexanucleotide GGCCTG is repeated 3 to 14 times within the gene. In people with SCA36, the GGCCTG sequence is repeated at least 650 times. It is unclear whether 15 to 649 repetitions of this hexanucleotide causes any signs or symptoms. Also, it is believed that the great expansion in the repetition hexanucleotídica NOP56 gene can reduce the activity of a nearby gene called MIR1292. The MIR1292 gene encodes a type of RNA that regulates the expression of genes encoding glutamate receptors. These proteins are found on the surface of neurons and permitenn these cells communicate with each other. A decrease in RNA production MIR1292 can lead to an increase in encoding glutamate receptors. The increased activity may overload receptor neurons, disrupting normal communication between cells and may contribute to ataxia. Because the NOP56 gene is particularly active in the cerebellar neurons, these cells are particularly affected by the expansion of the gene, leading to cerebellar atrophy. The deterioration in this part of the brain leads to ataxia and other signs and symptoms of SCA36.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person has a parent with the disease. In the disturbances caused by repeated DNA segments, often the number of repetitions is increased when the altered gene is passed from one generation to the next. In addition, a greater number of repetitions is usually associated with an earlier onset of signs and symptoms, a phenomenon known as anticipation.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with spinocerebellar ataxia type 36 (SCA36), by complete PCR amplification of the exons of the gene NOP56, 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).