Test Catalog

Test Id : SMNCS

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Spinal Muscular Atrophy Carrier Screening, Deletion/Duplication Analysis, Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

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

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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
A short description of the method used to perform the test

Dosage Analysis by Digital Droplet Polymerase Chain Reaction (ddPCR)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

SMA Carrier by Del/Dup

Aliases
Lists additional common names for a test, as an aid in searching

Spinal Muscular Atrophy Type I

SMA1

SMAI

SMA Infantile Acute Form

Muscular Atrophy, Infantile

Severe Infantile Acute Spinal Muscular Atrophy

Spinal Muscular Atrophy-1

Spinal Muscular Atrophy, Type II

SMA2

SMAII

Muscular Atrophy, Spinal, Intermediate Type

Muscular Atrophy, Spinal, Infantile Chronic Form

Infantile Chronic Spinal Muscular Atrophy

Spinal Muscular Atrophy-2

Spinal Muscular Atrophy, Type III

SMA3

SMAIII

Muscular Atrophy, Juvenile

Kugelberg-Welander Syndrome

KWS

Spinal Muscular Atrophy, Mild Childhood and Adolescent Form

Spinal Muscular Atrophy-3

Spinal Muscular Atrophy, Type IV

SMA4

SMAIV

Spinal Muscular Atrophy, Adult Form

Spinal Muscular Atrophy, Proximal, Adult, Autosomal Recessive

Adult-Onset SMA

Spinal Muscular Atrophy-4

SMA carrier screening

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Specimen Type
Describes the specimen type validated for testing

Varies

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

Blood: 1 mL

Tissue Biopsy: 200 mg

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

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

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. D'Amico A, Mercuri E, Tiziano FD, Bertini E: Spinal muscular atrophy. Orphanet J Rare Dis 2011;6:71

2. 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

3. Carre A, Empey C: Review of Spinal Muscular Atrophy (SMA) for Prenatal and Pediatric Genetic Counselors. 2016;25:32-43

4. Committee on Genetics: Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol 2017;129:e35-e40

5. Committee on Genetics: Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol March 2017;129;e41-e55

6. 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

7. Prior TW, Nagan N: Spinal muscular atrophy: overview of molecular diagnostic approaches. Curr Protoc Hum Genet 2016;1:88 unit 9.27

8. Prior TW, Nagan N, Sugarman EA, et al: Technical standards and guidelines for spinal muscular atrophy testing. Genet Med 2011;13:686-694

Method Description
Describes how the test is performed and provides a method-specific reference

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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

5 to 10 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • 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.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81329

88233 (if appropriate)

88240 (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
SMNCS SMA Carrier by Del/Dup 49857-6
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
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

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports