Test Id : SMNDX

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge.

If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added per laboratory protocol at an additional charge.

For any prenatal specimen that is received, maternal cell contamination testing will be added per laboratory protocol at an additional charge.

If the patient has abnormal newborn screening result for spinal muscular atrophy, immediate action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet(1).

The following algorithms are available:

-Inherited Motor Neuron Disease and Dementia Testing Algorithm

-Spinal Muscular Atrophy Testing Algorithm

All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Specimen preferred to arrive within 96 hours of collection.

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.

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.

Additional Information: To ensure a minimum DNA amount and concentration, the preferred blood volume must be submitted. Testing may be canceled if the specimen supplied is inadequate. 

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

Prenatal Specimens

Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor. 

Submit only 1 of the following specimens:

Specimen Type: Amniotic fluid

Container/Tube:

Preferred: Screw-capped, sterile centrifuge tubes

Acceptable: T-25 flasks of confluent cultured cells

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Specimen Type: Chorionic villi

Container/Tube:

Preferred: 15-mL tube containing 15 mL of transport media

Acceptable: T-25 flasks of confluent cultured cells

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Specimen Type: Blood spot

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Perkin Elmer 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 >1 year of age is a finger stick.

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. 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.

• Molecular Genetics: Congenital Inherited Diseases Patient Information
• Informed Consent for Genetic Testing
• Hereditary Peripheral Neuropathy Diagnostic Algorithm
• Blood Spot Collection Card-Spanish Instructions
• Blood Spot Collection Card-Chinese Instructions
• Inherited Motor Neuron Disease Testing and Dementia Algorithm
• Informed Consent for Genetic Testing (Spanish)
• Spinal Muscular Atrophy Testing Algorithm
• Blood Spot Collection Instructions

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.

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

Blood: 1 mL

Amniotic Fluid: 10 mL

Chorionic villi: 5 mg

First-tier newborn screening for spinal muscular atrophy (SMA)

Prenatal testing for SMA

Diagnostic testing to confirm a suspected diagnosis of SMA

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

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge.

If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added per laboratory protocol at an additional charge.

For any prenatal specimen that is received, maternal cell contamination testing will be added per laboratory protocol at an additional charge.

If the patient has abnormal newborn screening result for spinal muscular atrophy, immediate action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet(1).

The following algorithms are available:

-Inherited Motor Neuron Disease and Dementia Testing Algorithm

-Spinal Muscular Atrophy Testing Algorithm

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 and Genomics (ACMG) and The American Congress 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 less than 10% of residual SMN protein. This occurs because SMN2 differs from SMN1 by 5 nucleotide changes, one 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 alteration 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 or more SMN1 copies may, in fact, have 2 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 one copy of SMN1 on each chromosome. However, following a study performed by Luo et al,(2) 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 alteration g.27134T>G. The presence of this alteration 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. See the table below for details.

SMA carrier residual risk estimates.(2)

An interpretive report will be provided.

An interpretive report will be provided.

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.

1. Newborn Screening ACT Sheet [Exon 7 Deletion (Pathogenic Variant) in Survival Motor Neuron Gene (SMN1)] Spinal Muscular Atrophy (SMA). American College of Medical Genetics and Genomics; 2020. Accessed September 25, 2024. Available at www.acmg.net/PDFLibrary/SMA-ACT-Sheet.pdf

2. Luo M, Liu L, Peter I, et al: An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 2014;16:149-156. doi: 10.1038/gim.2013.84

3. Hendrickson BC, Donohoe C, Akmaev VR, et al: Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 2009;46:641-644. doi:10.1136/jmg.2009.066969

4. Carre A, Empey C: Review of spinal muscular atrophy (SMA) for prenatal and pediatric genetic counselors. J Genet Couns. 2016;25:32-43. doi:10.1007/s10897-015-9859-z

5. Committee on Genetics: Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol. 2017;129:e35-e40. doi:10.1097/AOG.0000000000001951

6. Committee on Genetics: Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol. March 2017;129;e41-e55. doi:10.1097/AOG.0000000000001952

7. D'Amico A, Mercuri E, Tiziano FD, Bertini E: Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71. doi: 10.1186/1750-1172-6-71

8. Prior TW, Nagan N: Spinal muscular atrophy: overview of molecular diagnostic approaches. Curr Protoc Hum Genet. 2016;1:88 unit 9.27. doi:10.1002/0471142905.hg0927s88

9. Prior TW, Nagan N, Sugarman EA, Batish SD, Braastad C: Technical standards and guidelines for spinal muscular atrophy testing. Genet Med, 2011;13:686-694. doi:10.1097/GIM.0b013e318220d523

Droplet digital polymerase chain reaction 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). Variant nomenclature is based on the following GenBank Accession numbers (build GRCh37 [hg19]): NM_022874.(Unpublished Mayo method)

Varies

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

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.

81329

88235 (if appropriate)

88240 (if appropriate)

88233 (if appropriate)

88240 (if appropriate)

81265 (if appropriate)