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Spinal Muscular Atrophy (SMA) Copy Number Analysis, Fetal
2013444
Ordering Recommendation

Prenatal diagnostic testing for spinal muscular atrophy (SMA) when both parents carry a deletion of SMN1 or have a previous child with SMA caused by a deletion of SMN1.

Mnemonic
SMA DD FE
Methodology
Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
Within 10 days
New York DOH Approval Status
This test is New York DOH approved.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Fetal Specimen: Two T-25 flasks at 80 percent confluency of cultured amniocytes. If the client is unable to culture amniocytes, this can be arranged by contacting ARUP Client Services at (800) 522-2787.
AND Maternal Cell Contamination Specimen
: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B). 
Specimen Preparation
Cultured Amniocytes: Fill flasks with culture media. Transport two T-25 flasks at 80 percent confluency of cultured amniocytes. Backup cultures must be retained at the client's institution until testing is complete.
Maternal Cell Contamination Specimen:
Transport 3 mL whole blood. (Min: 1 mL) 
Storage/Transport Temperature
Amniotic Fluid: Room temperature.
Cultured Amniocytes:
CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of shipment due to viability of cells.
Maternal Cell Contamination Specimen:
Room temperature. 
Unacceptable Conditions
 
Remarks
Maternal specimen is recommended for proper test interpretation. Order Maternal Cell Contamination. Patient History Form is available on the ARUP Web site or by contacting ARUP Client Services at (800) 522-2787. 
Stability
Fetal Specimen: Ambient: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Maternal Cell Contamination Specimen
: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable 
Reference Interval
By report
Interpretive Data
Background information for Spinal Muscular Atrophy (SMA) Copy Number Analysis, Fetal
Characteristics
: Spinal muscular atrophy (SMA) is the most common lethal genetic disease in children, and is characterized by progressive muscle weakness due to degeneration of the lower motor neurons. Onset ranges from before birth to adulthood and severity is highly variable. Individuals with SMA have no (zero) functioning copies of the SMN1 gene that produces survival motor neuron protein; most (95 percent) have homozygous loss of SMN1 due to deletion or gene conversion, while some (5 percent) have a sequence variant in one remaining copy of SMN1. The SMN2 gene, adjacent and highly homologous to SMN1, produces lower levels of survival motor neuron protein compared to SMN1. Disease severity has been shown to be modified by SMN2 gene copy number in some cases, but phenotype cannot be predicted with certainty. SMN2 copy number will be reported for individuals with zero copies of SMN1 or symptomatic individuals with one copy of SMN1.
Inheritance: Autosomal recessive
Cause
: Pathogenic mutations in the SMN1 gene.
Variants Tested: For copy number: SMN1 (NM_000344.3) exon 7 c.840C and exon 8 c.*239G, and SMN2 (NM_017411.3) exon 7 c.840T.
Clinical sensitivity: 95-98 percent in individuals affected with SMA.
Methodology: Multiplex probe ligation-dependent amplification (MLPA)
Analytical sensitivity and specificity: 99 percent.
Limitations
: Diagnostic errors can occur due to rare sequence variations. Single base pair substitutions, small deletions/duplications, regulatory region mutations, and deep intronic mutations will not be detected. This test is unable to determine chromosomal phase of SMN1 or SMN2 copies.
For quality assurance purposes, ARUP Laboratories will confirm the above result at no charge following delivery. Order Confirmation of Fetal Testing and include a copy of the original fetal report (or the mother's name and date of birth) with the test submission. Please contact an ARUP genetic counselor at (800) 242-2787 extension 2141 prior to specimen submission.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Components
Component Test Code*Component Chart NameLOINC
0050548Maternal Contamination Study Fetal Spec31208-2
0050612Maternal Contam Study, Maternal Spec31208-2
2013438SMA Copy Number, Symptoms75325-1
2013439SMA Copy Number, SMN1 Copies35462-1
2013440SMA Copy Number, SMN2 Copies54449-4
2013445SMA Copy Number, Specimen
2013446SMA Copy Number, Interp
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases