Spinocerebellar ataxia type 36

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What is spinocerebellar ataxia type 36?

Spinocerebellar ataxia type 36 (SCA36) is a condition characterized by progressive problems with movement that typically begin in mid-adulthood. People with this condition initially experience problems with coordination and balance (ataxia). Affected individuals often have exaggerated reflexes (hyperreflexia) and problems with speech (dysarthria). They also usually develop muscle twitches (fasciculations) of the tongue and over time, the muscles in the tongue waste away (atrophy). These tongue problems can cause difficulties swallowing liquids. As the condition progresses, individuals with SCA36 develop muscle atrophy in the legs, forearms, and hands. Another common feature of SCA36 is the atrophy of specialized nerve cells that control muscle movement (motor neurons), which can contribute to the tongue and limb muscle atrophy in affected individuals.

Some people with SCA36 have abnormalities of the eye muscles, which can lead to involuntary eye movements (nystagmus), rapid eye movements (saccades), trouble moving the eyes side-to-side (oculomotor apraxia), and droopy eyelids (ptosis). Sensorineural hearing loss, which is hearing loss caused by changes in the inner ear, may also occur in people with SCA36.

Brain imaging of people with SCA36 shows progressive atrophy of various parts of the brain, particularly within the cerebellum, which is the area of the brain involved in coordinating movements. Over time, the loss of cells in the cerebellum causes the movement problems characteristic of SCA36. In older affected individuals, the frontal lobes of the brain may show atrophy resulting in loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies.

Signs and symptoms of SCA36 typically begin in a person's forties or fifties but can appear anytime during adulthood. People with SCA36 have a normal lifespan and are usually mobile for 15 to 20 years after they are diagnosed.

How common is spinocerebellar ataxia type 36?

Approximately 100 individuals with SCA36 have been reported in the scientific literature. Almost all of these individuals have been from two regions: western Japan and the Costa de Morte in Galicia, Spain.

What genes are related to spinocerebellar ataxia type 36?

SCA36 is caused by mutations in the NOP56 gene. The NOP56 gene provides instructions for making a protein called nucleolar protein 56, which is primarily found in the nucleus of nerve cells (neurons), particularly those in the cerebellum. This protein is one part (subunit) of the ribonucleoprotein complex, which is composed of proteins and molecules of RNA, DNA's chemical cousin. The ribonucleoprotein complex is needed to make cellular structures called ribosomes, which process the cell's genetic instructions to create proteins.

The NOP56 gene mutations that cause SCA36 involve a string of six DNA building blocks (nucleotides) located in an area of the gene known as intron 1. This string of six nucleotides (known as a hexanucleotide) is represented by the letters GGCCTG and normally appears multiple times in a row. In healthy individuals, GGCCTG is repeated 3 to 14 times within the gene. In people with SCA36, GGCCTG is repeated at least 650 times. It is unclear if 15 to 649 repeats of this hexanucleotide cause any signs or symptoms.

To make proteins from the genetic instructions carried in genes, a molecule called messenger RNA (mRNA) is formed. This molecule acts as a genetic blueprint for protein production. However, a large increase in the number of GGCCTG repeats in the NOP56 gene disrupts the normal structure of NOP56 mRNA. Abnormal NOP56 mRNA molecules form clumps called RNA foci within the nucleus of neurons. Other proteins become trapped in the RNA foci, where they cannot function. These proteins may be important for controlling gene activity or protein production.

Additionally, researchers believe that the large expansion of the hexanucleotide repeat in the NOP56gene may reduce the activity of a nearby gene called MIR1292. The MIR1292 gene provides instructions for making a type of RNA that regulates the activity (expression) of genes that produce proteins called glutamate receptors. These proteins are found on the surface of neurons and allow these cells to communicate with one another. A decrease in the production of Mir1292 RNA can lead to an increase in the production of glutamate receptors. The increased receptor activity may overexcite neurons, which disrupts normal communication between cells and can contribute to ataxia.

The combination of RNA foci and overly excited neurons likely leads to the death of these cells over time. Because the NOP56 gene is especially active in neurons in the cerebellum, these cells are particularly affected by expansion of the gene, leading to cerebellar atrophy. Deterioration in this part of the brain leads to ataxia and the other signs and symptoms of SCA36.

How do people inherit spinocerebellar ataxia type 36?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person has one parent with the condition.

In conditions that are caused by repeated segments of DNA, the number of repeats often increases when the altered gene is passed down from one generation to the next. Additionally, a larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Some families affected by SCA36 have demonstrated anticipation while others have not. When anticipation is observed in SCA36, the mutation is most often passed down from the affected father.

Where can I find information about diagnosis or management of spinocerebellar ataxia type 36?

These resources address the diagnosis or management of spinocerebellar ataxia type 36 and may include treatment providers.

You might also find information on the diagnosis or management of spinocerebellar ataxia type 36 inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about spinocerebellar ataxia type 36?

You may find the following resources about spinocerebellar ataxia type 36 helpful. These materials are written for the general public.

Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page
Educational resources - Information pages (7 links)
Patient support - For patients and families (5 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary
Genetic Testing Registry - Repository of genetic test information (1 link)
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for spinocerebellar ataxia type 36?

Asidan ataxia
Costa de Morte ataxia
SCA36
spinocerebellar ataxia 36

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about spinocerebellar ataxia type 36?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding spinocerebellar ataxia type 36?

anticipation ; apraxia ; ataxia ; atrophy ; autosomal ; autosomal dominant ; cell ; cerebellum ; DNA ;dysarthria ; gene ; imaging ; inherited ; intron ; involuntary ; messenger RNA ; molecule ; motor ;mRNA ; mutation ; nucleus ; nystagmus ; protein ; ptosis ; receptor ; ribosomes ; RNA ;sensorineural ; sensorineural hearing loss ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (6 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.