Amyotrophic Lateral Sclerosis (ALS)

AMYOTROPHIC LATERAL SCLEROSIS (ALS)

Gene Symbol: SOD1

Chromosomal Locus: 21q22.11

Protein: Superoxide dismutase

Pseudonyms: Lou Gehrig Disease

TURNAROUND TIME: 4 weeks

TESTING METHODOLOGY: Polymerase chain reaction (PCR) and DNA Sequencing of all 5 exons, and their intron- exon borders.

SPECIMEN REQUIREMENTS:

Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
Min. Collection: 0.7 ml whole blood EDTA.
Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen at 40°C and ship Monday).
Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.

A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.

Note:

Counseling and informed consent are recommended for genetic testing; a Consent form is available as a resource, but not required.

INTERPRETATIVE DATA:

Incidence: approximately 4 to 8 in 100,000. Approximately 10% of all cases are familial (FALS).

Inheritance: Autosomal dominant in the familial form. Sporadic cases may be due to de novo mutations. ALS may also be acquired due to environmental exposures.

Disease Characteristics: Progressive adult-onset neurodegeneration involving both upper and lower motor neurons of the brain and spinal cord. Symptoms include weakness, stumbling, hyperreflexia, muscular atrophy and paralysis. The mean age onset of FALS (familial ALS) is age 46. Death usually results from compromise of the respiratory muscles.

Molecular Genetic Mechanism: A variety of missense, nonsense and insertion/deletion mutations have been described in the gene.

Clinical Sensitivity: 20% of cases of FALS and 3% of sporadic ALS cases will have an identifiable SOD1 mutation.

Analytic Sensitivity: 99%

Test Limitations: Deletions of the entire gene or mutations that are not in the sequenced segments of the SOD1 gene will not be detected.

INDICATIONS FOR USE:

To determine whether SOD1 is responsible for FALS in a patient.
SOD1 testing is appropriate in any individual with ALS who has another affected family member or an incomplete family history, including the early death of a close relative.

ADDITIONAL RESOURCES:

OMIM ALS1: www.omim.org/entry/105400

OMIM SOD1 Gene: www.omim.org/entry/147450

Gene Reviews: www.ncbi.nlm.nih.gov/pubmed/20301623

Genetics Home Reference: www.ghr.nlm.nih.gov/gene/SOD1