Test Code SOD1Z SOD1 Gene, Full Gene Analysis, Varies

Ordering Guidance

The recommended first tier test for amyotrophic lateral sclerosis is C9ORF / C9orf72 Hexanucleotide Repeat, Molecular Analysis, Varies.

Targeted testing (also called site-specific or known variants testing) is available for variants identified in the SOD1 gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Testing for the SOD1 gene as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Secondary ID

617740

Useful For

Establishing a molecular diagnosis for patients with amyotrophic lateral sclerosis (ALS)

Identifying variants within SOD1 known to be associated with ALS, allowing for predictive testing of at-risk family members

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

SOD1 Gene, Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with progressive loss of upper and lower motor neurons. ALS typically presents with progressive muscle wasting, hyperreflexia, and spasticity. Death from respiratory failure usually occurs within 3 to 5 years of disease onset.

The SOD1 gene is the second most commonly known cause of familial ALS (fALS) and is reported to occur in around 12% of fALS cases. Variants in SOD1 are believed to cause ALS through a toxic gain-of-function caused by aggregation of misfolded SOD1 protein. Although most cases of SOD1-related fALS are inherited in an autosomal dominant manner, rare cases with autosomal recessive inheritance have been reported.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of SOD1, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in SOD1.

There may be regions of SOD1 that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)

The reference transcript for SOD1 gene is NM_000454.4. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing.

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Day(s) Performed