Amyotrophic Lateral Sclerosis (ALS): SOD1, FUS, TARDBP Sequencing

Diagnostic Use

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of motor neurons in the motor cortex, brain stem, and spinal cord. The dysfunction and loss of these neurons results in muscle weakness, atrophy and eventually paralysis of limb, bulbar and respiratory muscles. The prevalence of ALS is 1-9 per 100,000. A majority of ALS occurs in individuals with no family history of ALS. Familial ALS is most frequently inherited in an autosomal dominant disorder. Less frequently, it can be inherited in an autosomal recessive or X-linked fashion.
The four genes most commonly implicated in familial ALS are C9orf72, SOD1, FUS and TARDBP (PMID 20301623). This gene panel covers SOD1, FUS and TARDBP, whilst C9orf72 is available as a separate test.
Pathogenic variants in SOD1 are implicated in 15-20% of familial ALS, and in 3% of sporadic ALS. Patients with a pathogenic SOD1 variant are expected to respond to SOD1-targeted therapy (Tofersen), which has recently been approved by the FDA.
Note that this ALS gene panel will analyse and report the results for all three genes (SOD1, FUS, TARDBP).

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

Motor neuron disease
MND

Turnaround Time

4 weeks

Test Code

4583

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Additional Specimen Information

If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

After extraction of DNA from the peripheral blood sample, the DNA is analysed using a Twist Biosciences next generation sequencing  (NGS) custom panel on an Illumina MiSeq instrument. The panel targets the  following genes that have been implicated in familial ALS: SOD1 (NM_000454.5), FUS (NM_004960.4), TARDBP (NM_007375.4).  All coding regions and intron-exon boundaries are analysed to a minimum read depth of 30x. Copy number variants (CNVs) in the genes listed above are assessed by analysis of coverage depth data from the Twist NGS panel using a validated in-house algorithm.

Non-Funded Test Cost

$694.39 (Exclusive of GST)

Billing Code

4583

Uncertainty of Measurement:
Next generation DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Contact Information

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