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Test Code SMNCS Spinal Muscular Atrophy Carrier Screening, Deletion/Duplication Analysis, Varies


Additional Testing Requirements


 



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 Mayo Clinic Laboratories 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 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.

 

Specimen Type: Blood spot

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

 

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 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. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions

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

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

 

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

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

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

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Tissue biopsy

Supplies: Muscle Biopsy Kit (T541)

Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation Instructions.

Additional Information: Muscle Biopsy Shipping Kits (T541) are available.

Specimen Volume: 10-80 mg

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated


Useful For

General population carrier screening for spinal muscular atrophy (SMA)

 

Carrier screening for reproductive partners of known SMA carriers

 

Carrier screening for parents of a child with a known deletion of the survival motor neuron 1 gene (SMN1) or other family history of SMA

Genetics Test Information

SMN1 exon 7 copy number and SMN2 exon 7 copy number are determined. Also ascertains whether the g.27134T>G polymorphism is present or absent in patients found to have 2 copies of SMN1.

Reflex Tests

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

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Method Name

Dosage Analysis by Digital Droplet Polymerase Chain Reaction (ddPCR)

Reporting Name

SMA Carrier by Del/Dup

Specimen Type

Varies

Specimen Minimum Volume

Blood: 1 mL
Tissue Biopsy: 200 mg

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

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

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) and The American College of Obstetricians and Gynecologists (ACOG) currently recommend 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 SMN1 gene but a small portion of SMN is also contributed by the SMN2 gene. In fact, SMN1 produces more than 90% of SMN protein, while SMN2 produces about less than 10% of residual SMN protein. This occurs because SMN2 differs from SMN1 by 5 nucleotide changes, 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 have been observed. 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 point mutation in the other allele. The severity of a patient's disease 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.

 

As the SMA test is a quantitative assay for the number of SMN1 exon 7 deletions, any result showing 2 SMN1 copies may in fact have 2 normal copies of SMN1 in cis (on the same chromosome) and a copy of SMN1 with the exon 7 deletion on the other chromosome (in trans). This is called the "2+0" carrier genotype. The frequency of the "2+0" carrier genotype differs by ancestry. Previously, it was not possible to distinguish a "2+0" carrier from an individual with 1 copy of SMN1 on each chromosome. However, following a study performed by Luo et al,(6) it is now possible to provide an adjusted genetic residual carrier risk specific to one’s ancestry, based on the presence or absence of the SMN1 polymorphism g.27134T>G. The presence of this polymorphism is linked to being a "2+0" carrier in the Ashkenazi Jewish and Asian populations and it increases the chances that one is a "2+0" carrier in other populations. Please see the table below for details.

 

SMA carrier residual risk estimates.(6)  

Ancestry

Carrier frequency

Detection rate based on copy number alone

Residual risk after detection of 2 copies of SMN1

Detection rate with addition of SMN1 g.27134T>G

Residual risk  of being a 2+0 carrier after absence of SMN1 g.27134T>G

Residual risk of being a 2+0 carrier after presence of SMN1 g.27134T>G

Ashkenazi Jewish

1 in 41.1

90%

1 in 345

94%

1 in 580

2+0 Carrier

Asian

1 in 53

92.6%

1 in 628

93.3%

1 in 701.8

2+0 Carrier

African American

1 in 66

71.1%

1 in 121

N/A

1 in 395.7

1 in 33.5

Hispanic

1 in 117

90.6%

1 in 1,061

N/A

1 in 1,762

1 in 139.6

European

1 in 35

94.9%

1 in 632

N/A

1 in 769.3

1 in 28.6

 

Reference Values

An interpretive report will be provided.

Interpretation

An interpretive report will be provided.

Cautions

Point mutations are undetectable by this assay. Nor can this assay definitively discriminate between 2 copies of survival motor neuron 1 (SMN1) on the same chromosome versus 2 copies on separate chromosomes for patients of most ancestries.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match clinical findings, additional testing should be considered.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Method Description

Droplet digital PCR method for detection and quantification of survival motor neuron 1 (SMN1) exon 7, SMN2 exon 7, and SMN1 rs143838139 (g.27134T>G) associated with spinal muscular atrophy (SMA). Mutation nomenclature is based on the following GenBank Accession numbers (build GRCh37 [hg19]): NM_022874.(Unpublished Mayo method)

Day(s) Performed

Varies

Report Available

5 to 10 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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

CPT Code Information

81329

88233 (if appropriate)

88240 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SMNCS SMA Carrier by Del/Dup 49857-6

 

Result ID Test Result Name Result LOINC Value
113445 Result Summary 50397-9
113446 Result 49857-6
113447 Interpretation 69047-9
113448 Additional Information 48767-8
113449 Specimen 31208-2
113450 Source 31208-2
113451 Released By 18771-6