EXP​ – Expansion Repeats

Expansion repeats testing is indicated when individuals present with diagnostic or clinical symptoms relating to diseases caused by expansion repeats. This test can be offered in all life stages depending on clinical presentation

The most common genetic disorders detected by Expansion repeat testing include:

• CAG/polyQ diseases
• Spinocerebellar ataxia types SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12, SCA31, SCA10
• C9ORF72 frontotemporal dementia/ amyotrophic lateral sclerosis
• Huntington disease
• Myotonic dystrophy types 1 and 2
• Oculopharyngeal muscular dystrophy
• Fragile X tremor ataxia syndrome
• Friedreich Ataxia
• Fragile X syndrome
• Myoclonic epilepsy

Depending on the type of suspected disorder there are different types of PCR tests that can be offered.

• When disorder is caused by a small number of repeats (< 50 repeats), amplification primers encompass the repeat.
• When a disorder is caused by a large number of repeats (>100 repeats), that conventional PCR cannot amplify. Amplification primers encompass the repeat and include the repeated sequence.

• Negative Result

  A negative results indicates that the individual has the normal alleles repeats in the target gene and is not at an increased risk of developing the disorder.

• Premutation Alleles:

  A pre-mutation is a change that is of intermediate risk or in a “grey area”. Individuals with pre-mutations have a higher than normal number of repeat expansion but less than the number expected of the full mutation. The risk of an individual with a pre-mutation is variable and these pre-mutations are identified in such a manner because there is a small chance that they are unstable and may expand to a full mutation in future generations. There is no reported risk for an individual with an intermediate sized allele to have a child with a full mutation. Traditionally, a carrier of a genetic mutation is defined as a person who inherits an altered form of a gene but shows no effects of that mutation. However, this does not necessarily apply in cases with expansion repeats as depending on the condition, individuals with a pre-mutation might present with symptoms.

• Full mutation/ Disease-Causing Alleles:

  A result of a full mutation indicates that the individual has the expansion repeats that would cause genetic disease and this individual is likely to have symptoms of the disorder. Reduce penetrance plays a role in some expansion repeat diseases and so individuals with the full mutation may have variable symptoms depending on the condition in question.