- Repeat expansions are common genetic variations that are usually associated to neurogenetic disorders. These types of mutations are unstable and dynamic, and the number of repeats can change from generation to generation.
- Conditions that are caused by repeat expansions are clinically and genetically heterogeneous and vary depending on the repeat sequence, size and location within the disease gene, and whether the repeat is translated into protein.
- PCR-based analysis of repeat lengths is the most cost-effective method for the diagnosis of diseases associated with expansion repeats.
EXP – Expansion Repeats
Repeat expansion analysis can be requested for:
- Diagnosis of a patient suspected to have a genetic disorder that could be caused by a repeat expansion mutation.
- Carrier status for repeat expansions associated to autosomal recessive or X linked diseases.
- Presymptomatic diagnosis of at risk relatives with late onset diseases caused by repeat expansion mutation.
Some of the most common genetic disorders detected by Expansion repeat testing include:
- Fragile X syndrome and related conditions
- Friedreich Ataxia
- Huntington disease
- Myotonic dystrophy types 1 and 2
- Spinocerebellar ataxias
Depending on the type of suspected disorder there are different types of PCR tests that can be offered.
- PCR amplification encompassing the repeat when disorders are caused by a small number of repeats (< 50 repeats)
- TP-PCR, (triplet repeat primed PCR) when disorders are caused by a large number of repeats (>100 repeats) that conventional PCR cannot amplify. Amplification primers encompass the repeat and include the repeated sequence.
Reporting & Results
The number of repeats, clinical size ranges and inheritance patterns varies from disease to disease.
- Normal alleles Alleles with a number of repeats corresponding to the normal range for that disease are not pathogenic and the patient is not at an increased risk of developing the disorder, depending on the mode of inheritance.
- Premutation Alleles: Alleles with a number of repeats corresponding to the pre-mutation range are usually not pathogenic, but these alleles are usually unstable and may expand to a full and pathogenic mutation in future generations.
Depending on the disease and mode of inheritance, some individuals with a pre-mutation might present with symptoms.
- Full mutation/ Disease-Causing Alleles:
Alleles with a number of repeats corresponding to the full-mutation range are pathogenic and would cause the genetic disease, depending on the disease and mode of inheritance. The age-at-onset and severity of symptoms might vary depending on the number of repeats.
Sample Requirements
For Prenatal Diagnosis:
- Previous contact with the laboratory is strongly recommended to properly plan the case, prenatal deadlines and anticipate possible inconvenients.
- Maternal blood sample must be sent with all products of conception, CVS and Amnio samples.
- Pirority will be given to all prenatal samples.
A thorough labelling of the tube with unique identifying information is mandatory, incorrect labelling can lead to rejection of the sample. The minimum required information to identify and accept a sample is – Patient’s full name, Date of birth, Gender and Medical Record Number.
The ‘informed consent’ form and the ‘test requisition from’ must be properly filled-in and signed by the patient and doctor.
Limitations
- The scope of this assay is limited to the repeat expansion analysis of the targeted gene and may not reveal the exact number of repeats present in large expansions.
- Gene sequencing and deletion/duplication analysis are not included in this assay but can be ordered separately.
- This analysis does not include methylation studies.
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