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Test ID SMN1Z SMN1 Gene, Full Gene Analysis, Varies


Advisory Information


This is not the preferred genetic test for carrier screening or diagnosis in individuals with suspicion of spinal muscular atrophy. For these situations, order SMNCS / Spinal Muscular Atrophy Carrier Screening by Deletion/Duplication Analysis or SMNDX / Spinal Muscular Atrophy Diagnostic Assay by Deletion/Duplication Analysis.

 

This test is appropriate for second-tier carrier screening following SMNCS / Spinal Muscular Atrophy Carrier Screening by Deletion/Duplication Analysis when:

-There is a family history of spinal muscular atrophy (SMA), but an affected individual is not available for testing

-The disease-causing mutations are unknown

-Testing the reproductive partner of a known SMA carrier



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. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: 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 specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Supplies: Fibroblast Biopsy Transport Media (T115)

Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Supplies: Card - Blood Spot Collection (Filter Paper) (T493)

Specimen Type: Blood spot

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card (T493)

Specimen Volume: 5 Blood spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card)

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions.

Useful For

Confirming a diagnosis of spinal muscular atrophy due to nucleotide variants in SMN1 gene

 

Second-tier carrier screening when there is a family history of spinal muscular atrophy, but an affected individual is not available for testing, or when disease-causing mutations are unknown

 

Second-tier carrier screening for the reproductive partner of a known SMA carrier

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

If skin biopsy is received, fibroblast culture will be added and charged separately.

 

See Inherited Motor Neuron Disease Testing Algorithm in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

SMN1 Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

Blood: 1 mL
Blood Spots: 3 punches 3-mm diameter

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by motor neuron degeneration leading to muscular atrophy with progressive paralysis. It is a genetically complex condition that is traditionally divided into 5 subtypes, depending on the age at which symptoms present and the motor milestones that are achieved. Presentation can range from in utero joint contractures and lack of fetal movement (type 0), to loss of ambulation in adolescence or adulthood (type IV). All patients with SMA develop symmetrical loss of muscle control, most commonly affecting proximal muscles. The American College of Medical Genetics (ACMG) recommends offering SMA carrier screening to all couples, regardless of race or ethnicity, before conception or early in pregnancy.

 

The most common form of SMA is associated with the loss of survival motor neuron (SMN) protein, which is encoded by 2 or more genes on chromosome 5. The majority of SMN protein is expressed by the survival motor neuron 1 (SMN1) gene, but a small portion of SMN is also contributed by the survival motor neuron 2 (SMN2) gene. Indeed, SMN1 produces more than 90% of SMN protein, while SMN2 produces less than 10% of residual SMN protein. This occurs because SMN2 differs from SMN1 by 5 nucleotides, 1 of which leads to alternative exon 7 splicing, and a reduction of SMN2 expression. Most individuals have 2 copies of SMN1, but individuals with as many as 5 copies of SMN1 are detected. In addition, individuals may also have 0 to 5 copies of SMN2.

 

SMA is most commonly caused by a homozygous deletion of exon 7 in SMN1. However, some patients with this disorder may be compound heterozygotes, with a deletion of 1 copy of SMN1 and a nucleotide variant in the other allele. The severity of a patient's disease course is associated with the number of copies of SMN2 that are present, and 3 or more SMN2 copies are associated with a milder SMA phenotype.

 

This test aims to specifically identify nucleotide variants in SMN1 by direct sequencing and to distinguish these nucleotide variants from changes within SMN2. However, SMN1 exon 1 variants are still unable to be distinguished from changes within SMN2 exon 1.

Reference Values

An interpretive report will be provided.

Interpretation

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

Clinical Reference

1. Wirth B: An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat 2000;15:228-237

2. Clermont O, Burlet P, Benit P, et al: Molecular analysis of SMA patients without homozygous SMN1 deletions using a new strategy for identification of SMN1 subtle mutations. Hum Mutat 2004;24:417-427

3. Kubo Y, Nishio H, Saito K: A new method for SMN1 and hybrid SMN gene analysis in spinal muscular atrophy using long-range PCR followed by sequencing. J Hum Genet 2015;60: 233-239

4. Prior T, Finanger E: Spinal Muscular Atrophy. Gene Reviews. Update Dec 22, 2016. Available at www.ncbi.nlm.nih.gov/sites/books/NBK1352/

5. The Human Gene Mutation Database (HGMD), Professional version 2017.2 from BIOBASE. A database of germline mutations in genes associated with human inherited disease. Accessed Sep 12, 2017. Available at https://portal.biobase-international.com/hgmd/pro/start.php 

Day(s) and Time(s) Performed

Performed weekly; Varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81336

88233 (if appropriate)

88240 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SMN1Z SMN1 Full Gene Analysis 94221-9

 

Result ID Test Result Name Result LOINC Value
602754 Result Summary 50397-9
602755 Result 82939-0
602756 Interpretation 69047-9
602757 Additional Information 48767-8
602758 Specimen 31208-2
602759 Source 31208-2
602760 Released By 18771-6