Performed

Monday - Friday

Methodology

Allele Specific Multiplexed Real-Time Polymerase Chain Reaction

Reported

Routine: 7 days

Synonyms

  • SMA Copy Number
  • Survival Motor Neuron 1 Gene
  • Survival Motor Neuron 2 Gene
  • SMN1 Gene
  • SMN2 Gene
  • Inherited Disease
  • Clinical Genomics

Performing Lab

Clinical Genomics

Turnaround Time

12 days

Add-on Eligibility

Yes, within 7 days of collection
*If DNA has been extracted previously for other Clinical Genomics tests, this is stored for 6 weeks and may qualify for add-on

Specimen Type

Blood

Specimen Volume

5 mL (Minimum: 1 mL)

Collection Container

EDTA Whole Blood Tube (Lavender Top Vacutainer)

Unacceptable Conditions

  1. Severely clotted or grossly hemolyzed specimens
  2. Specimens that have been improperly collected, stored, or transported
  • Specimens collected in preservatives other than EDTA
    • ACD tubes are accepted, but EDTA is preferred
  • Serum or plasma
  • Specimens that have been frozen
  • Commingled specimens
  1. Specimens in tubes that have been damaged or broken during transport
  2. Specimens with insufficient volume for testing
  3. Unlabeled or mislabeled specimens

Storage/Transport Temperature

Transport Instructions      
Collection Location Transport Temperature Processing Required Timeframe
ED/Inpatient Room Temperature None Specimen must be received by the lab within 3 days of collection
Laboratory/Outpatient/Off-Site Room Temperature None Specimen must be received by the lab within 3 days of collection

Storage: Refrigerated

Stability (from collection to initiation)

Stability:
Prior to Extraction:
  • Room Temperature: 3 days
  • Refrigerated: 7 days
  • Frozen: Unacceptable
Extracted DNA:
  • Room Temperature: Unacceptable
  • Refrigerated: Unacceptable
  • Frozen: Indefinitely

Laboratory Storage: 
  • Original Specimen: Refrigerated
  • Extracted DNA: Frozen
Laboratory Retention: 
  • Original Specimen: 6 weeks
  • Extracted DNA: 6 weeks

Collection Instructions

Labeling Instructions:
When labeling blood tubes, leave a small window visible for the lab to assess the fill volume and sample integrity. Ensure that the barcode is in the correct orientation.


Collection Instructions:
Follow the correct order of draw when collecting with additional orders and tube types:
     
 

Reference Interval

SMN1 Copy Number: 2
SMN2 Copy Number: 2
Linked Variant: Absent

Interpretive Data

Refer to report for result specific interpretation details.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by loss of survival motor neuron 1 (SMN1) gene function, and is the most common lethal genetic disease in children characterized by progressive muscle weakness due to degeneration of the alpha motor neurons in the spinal cord. Onset ranges from before birth to adulthood and severity is highly variable. SMA has an incidence of ~1/10,000 live births and a carrier rate of ~1/50, varying by ethnicity. Individuals with SMA have no functioning copies of the SMN1 gene. Most SMA cases (95%) have a loss of both copies of the SMN1 gene due to deletion or gene conversion ("hybrid" genes), while a minority (5%) have a deletion of SMN1 on one chromosome and an SMN1 sequence variant on the other. 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, though phenotype cannot be predicted with certainty. Disease severity has also been shown to be associated with a single base substitution in SMN2, c.859G>C, which results in less severe phenotypes in those affected with SMA. Two variants in SMN1, c.*3+80T>G and c.*211_*212del, are part of a haplotype associated with SMN1 duplication in silent carriers (two copies of SMN1 on one chromosome and no copies on the other), particularly in individuals of Ashkenazi Jewish descent. The presence of a linked variant increases the likelihood that two copies of SMN1 are on the same chromosome in certain ethnic groups.

Methodology: Multiplexed PCR Assay to amplify exon 7 of the SMN1 and SMN2 genes

Limitations: 
  1. Diagnostic error may occur with this test due to rare genetic variation at a primer binding site. This test is specific for quantifying exon 7 genomic copy number of the SMN1 and SMN2 genes, respectively.
  2. Nonsense, frameshift, or missense mutations will not be detected.
  3. This assay cannot discriminate between two copies of SMN1 on the same chromosome ([2+0] or silent carriers) versus two copies on separate chromosomes [1+1]; however, linked variants associated with [2+0] silent carriers may be informative in some populations.
  4. This assay identifies the presence of hybrid genes, which are included and reported in the total SMN1 and SMN2 copy number count. This assay cannot determine whether these hybrid genes occur on the same or opposite chromosome as the other SMN1 copies.

This test was adopted and its performance characteristics determined by the UC San Diego Health System Molecular Diagnostics Laboratory. It has not been cleared or approved by the Food and Drug Administration (FDA). FDA clearance or approval is not required for clinical use. The result of this test should be interpreted using all relevant clinical data and should not be used alone for clinical diagnosis or patient management decisions. 
Ordering

Performed

Monday - Friday

Methodology

Allele Specific Multiplexed Real-Time Polymerase Chain Reaction

Reported

Routine: 7 days

Synonyms

  • SMA Copy Number
  • Survival Motor Neuron 1 Gene
  • Survival Motor Neuron 2 Gene
  • SMN1 Gene
  • SMN2 Gene
  • Inherited Disease
  • Clinical Genomics

Performing Lab

Clinical Genomics

Turnaround Time

12 days

Add-on Eligibility

Yes, within 7 days of collection
*If DNA has been extracted previously for other Clinical Genomics tests, this is stored for 6 weeks and may qualify for add-on
Collection

Specimen Type

Blood

Specimen Volume

5 mL (Minimum: 1 mL)

Collection Container

EDTA Whole Blood Tube (Lavender Top Vacutainer)

Unacceptable Conditions

  1. Severely clotted or grossly hemolyzed specimens
  2. Specimens that have been improperly collected, stored, or transported
  • Specimens collected in preservatives other than EDTA
    • ACD tubes are accepted, but EDTA is preferred
  • Serum or plasma
  • Specimens that have been frozen
  • Commingled specimens
  1. Specimens in tubes that have been damaged or broken during transport
  2. Specimens with insufficient volume for testing
  3. Unlabeled or mislabeled specimens

Storage/Transport Temperature

Transport Instructions      
Collection Location Transport Temperature Processing Required Timeframe
ED/Inpatient Room Temperature None Specimen must be received by the lab within 3 days of collection
Laboratory/Outpatient/Off-Site Room Temperature None Specimen must be received by the lab within 3 days of collection

Storage: Refrigerated

Stability (from collection to initiation)

Stability:
Prior to Extraction:
  • Room Temperature: 3 days
  • Refrigerated: 7 days
  • Frozen: Unacceptable
Extracted DNA:
  • Room Temperature: Unacceptable
  • Refrigerated: Unacceptable
  • Frozen: Indefinitely

Laboratory Storage: 
  • Original Specimen: Refrigerated
  • Extracted DNA: Frozen
Laboratory Retention: 
  • Original Specimen: 6 weeks
  • Extracted DNA: 6 weeks

Collection Instructions

Labeling Instructions:
When labeling blood tubes, leave a small window visible for the lab to assess the fill volume and sample integrity. Ensure that the barcode is in the correct orientation.


Collection Instructions:
Follow the correct order of draw when collecting with additional orders and tube types:
     
 
Result Interpretation

Reference Interval

SMN1 Copy Number: 2
SMN2 Copy Number: 2
Linked Variant: Absent

Interpretive Data

Refer to report for result specific interpretation details.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by loss of survival motor neuron 1 (SMN1) gene function, and is the most common lethal genetic disease in children characterized by progressive muscle weakness due to degeneration of the alpha motor neurons in the spinal cord. Onset ranges from before birth to adulthood and severity is highly variable. SMA has an incidence of ~1/10,000 live births and a carrier rate of ~1/50, varying by ethnicity. Individuals with SMA have no functioning copies of the SMN1 gene. Most SMA cases (95%) have a loss of both copies of the SMN1 gene due to deletion or gene conversion ("hybrid" genes), while a minority (5%) have a deletion of SMN1 on one chromosome and an SMN1 sequence variant on the other. 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, though phenotype cannot be predicted with certainty. Disease severity has also been shown to be associated with a single base substitution in SMN2, c.859G>C, which results in less severe phenotypes in those affected with SMA. Two variants in SMN1, c.*3+80T>G and c.*211_*212del, are part of a haplotype associated with SMN1 duplication in silent carriers (two copies of SMN1 on one chromosome and no copies on the other), particularly in individuals of Ashkenazi Jewish descent. The presence of a linked variant increases the likelihood that two copies of SMN1 are on the same chromosome in certain ethnic groups.

Methodology: Multiplexed PCR Assay to amplify exon 7 of the SMN1 and SMN2 genes

Limitations: 
  1. Diagnostic error may occur with this test due to rare genetic variation at a primer binding site. This test is specific for quantifying exon 7 genomic copy number of the SMN1 and SMN2 genes, respectively.
  2. Nonsense, frameshift, or missense mutations will not be detected.
  3. This assay cannot discriminate between two copies of SMN1 on the same chromosome ([2+0] or silent carriers) versus two copies on separate chromosomes [1+1]; however, linked variants associated with [2+0] silent carriers may be informative in some populations.
  4. This assay identifies the presence of hybrid genes, which are included and reported in the total SMN1 and SMN2 copy number count. This assay cannot determine whether these hybrid genes occur on the same or opposite chromosome as the other SMN1 copies.

This test was adopted and its performance characteristics determined by the UC San Diego Health System Molecular Diagnostics Laboratory. It has not been cleared or approved by the Food and Drug Administration (FDA). FDA clearance or approval is not required for clinical use. The result of this test should be interpreted using all relevant clinical data and should not be used alone for clinical diagnosis or patient management decisions. 

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