Ordering Recommendations

Use to confirm a suspected diagnosis of spinal muscular atrophy (SMA) and quantify SMN2 copy number for treatment purposes in affected individuals. Use for prenatal or preconception carrier screening for SMA in the general population, carrier screening for the reproductive partner of a known SMA carrier, and carrier screening for parents of a child with a deletion of the SMN1 gene or other family history of SMA.

Available Stat

No

Performing Lab

ARUP

Performed

Varies

Methodology

Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reported

7-14 days

Additional Technical Information

Additional Information

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier rate of about 1 in 50 in the US, leading to disease in approximately 1 in 10,000 live births. SMA is a neuromuscular disorder and a frequently inherited cause of infant mortality. SMA is characterized by degeneration of lower motor neurons in the spinal cord and brain stem, leading to muscle wasting and paralysis. The disorder is classified into four subtypes (I-IV) based on the age of onset, which can range from infancy to adulthood. In its most severe form (Type I), SMA leads to death in infancy. In other non-fatal forms, affected individuals become disabled. Treatment in these cases is aimed at slow progression of the disease. 

SMN1 Copy Number Assay
SMA is most often caused by deletions in theSMN1 gene and thus molecular testing assesses the number of copies of SMN1. Individuals affected with SMA have 0 copies of the SMN1 gene, whereas individuals with 1 copy of the SMN1 gene are predicted to be carriers of SMA. Individuals with 2 or more copies have a reduced risk to be carriers, namely because individuals, who are carriers of SMA as a result of either 2 or 3 copies of SMN1 on one chromosome and the absence of SMN1 on the other chromosome (termed as 2+0 or 3+0) cannot be detected by this assay. The 2+0 genotype occurs in about 3-4% of the general population. This assay will determine SMN1 copy number, but will not detect intragenic mutations within theSMN1gene.

SMN1 Linked Variants Assay
Duplication of SMN1 has been linked to a haplotype that spans two linked variants (rs143838139 and rs200800214). The presence of these two variants, especially in Ashkenazi Jews and Asians, increases the likelihood of a 2+0 SMN1 genotype, but does not confirm it. This assay will also determine the presence or absence of these two linked variants. Carrier risks estimation based on SMN1 copy number analysis and detection of the linked variants is shown in the Table below.

SMN2 Copy Number Assay
SMN2 is adjacent to SMN1 on chromosome 5 and differs from it by only a few bases. However, SMN2 expresses only about 10% of functional mRNA due to a defect in RNA splicing. Individuals can carry multiple copy numbers of SMN2, ranging from 0 to 5 copies per chromosome. Thus, the presence of multiple copy numbers of SMN2 with 0 copy SMN1 is associated with reduced severity of SMA, thereby accounting for the various SMA phenotypic subtypes. This assay will also determine SMN2 copy number.
 
Ethnic
Group		 Prior Risk CN
Detect. Rate		 CN3
Res. Risk		 CN2+NEG LV
Res. Risk		 CN2+POS LV
Res. Risk
Caucasian 1 in 35 95% 1 in 3,500 1 in 769 1 in 29
Ashkenazi Jewish 1 in 41 90% 1 in 4,000 1 in 580 Likely Carrier
Asian 1 in 53 93% 1 in 5,000 1 in 702 Likely Carrier
African American 1 in 66 71% 1 in 3,000 1 in 396 1 in 34
Hispanic 1 in 117 91% 1 in 11,000 1 in 1762 1 in 140
 
  1. Hendrickson BC et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641–644, 2009
  2. Ogino S et al. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet; 110:301-317, 2002
  3. Prior TW et al. Technical standards and guidelines for spinal muscular atrophy testing. Genet in Med. 13:686-694, 2011
  4. Luo M et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-156, 2013
  5. Sugarman EA et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 27-32, 2012
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy
  • SMA
  • SMN1
  • SMN2
  • Spinal Muscular Atrophy

Sample Type

EDTA whole blood

Label Abbreviation

SMA

Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B)

Stability (from collection to initiation)

Room Temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Storage/Transport Temperature

Refrigerated. Also acceptable: Ambient.

Test Code

UCSF Test Code LAB4259

ARUP Test Code

2013436

Sendout

Yes, ARUP

Performing Lab

ARUP

Specimen Preparation

Transport 2 mL whole blood. (Min: 1 mL)

Stability (from collection to initiation)

Room Temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Storage/Transport Temperature

Refrigerated. Also acceptable: Ambient.

Reference Interval

By report

Additional Information

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier rate of about 1 in 50 in the US, leading to disease in approximately 1 in 10,000 live births. SMA is a neuromuscular disorder and a frequently inherited cause of infant mortality. SMA is characterized by degeneration of lower motor neurons in the spinal cord and brain stem, leading to muscle wasting and paralysis. The disorder is classified into four subtypes (I-IV) based on the age of onset, which can range from infancy to adulthood. In its most severe form (Type I), SMA leads to death in infancy. In other non-fatal forms, affected individuals become disabled. Treatment in these cases is aimed at slow progression of the disease. 

SMN1 Copy Number Assay
SMA is most often caused by deletions in theSMN1 gene and thus molecular testing assesses the number of copies of SMN1. Individuals affected with SMA have 0 copies of the SMN1 gene, whereas individuals with 1 copy of the SMN1 gene are predicted to be carriers of SMA. Individuals with 2 or more copies have a reduced risk to be carriers, namely because individuals, who are carriers of SMA as a result of either 2 or 3 copies of SMN1 on one chromosome and the absence of SMN1 on the other chromosome (termed as 2+0 or 3+0) cannot be detected by this assay. The 2+0 genotype occurs in about 3-4% of the general population. This assay will determine SMN1 copy number, but will not detect intragenic mutations within theSMN1gene.

SMN1 Linked Variants Assay
Duplication of SMN1 has been linked to a haplotype that spans two linked variants (rs143838139 and rs200800214). The presence of these two variants, especially in Ashkenazi Jews and Asians, increases the likelihood of a 2+0 SMN1 genotype, but does not confirm it. This assay will also determine the presence or absence of these two linked variants. Carrier risks estimation based on SMN1 copy number analysis and detection of the linked variants is shown in the Table below.

SMN2 Copy Number Assay
SMN2 is adjacent to SMN1 on chromosome 5 and differs from it by only a few bases. However, SMN2 expresses only about 10% of functional mRNA due to a defect in RNA splicing. Individuals can carry multiple copy numbers of SMN2, ranging from 0 to 5 copies per chromosome. Thus, the presence of multiple copy numbers of SMN2 with 0 copy SMN1 is associated with reduced severity of SMA, thereby accounting for the various SMA phenotypic subtypes. This assay will also determine SMN2 copy number.
 
Ethnic
Group		 Prior Risk CN
Detect. Rate		 CN3
Res. Risk		 CN2+NEG LV
Res. Risk		 CN2+POS LV
Res. Risk
Caucasian 1 in 35 95% 1 in 3,500 1 in 769 1 in 29
Ashkenazi Jewish 1 in 41 90% 1 in 4,000 1 in 580 Likely Carrier
Asian 1 in 53 93% 1 in 5,000 1 in 702 Likely Carrier
African American 1 in 66 71% 1 in 3,000 1 in 396 1 in 34
Hispanic 1 in 117 91% 1 in 11,000 1 in 1762 1 in 140
 
  1. Hendrickson BC et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641–644, 2009
  2. Ogino S et al. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet; 110:301-317, 2002
  3. Prior TW et al. Technical standards and guidelines for spinal muscular atrophy testing. Genet in Med. 13:686-694, 2011
  4. Luo M et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-156, 2013
  5. Sugarman EA et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 27-32, 2012
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.

Additional Technical Information

Interpretive Data

Refer to report.

CPT Codes

81329

LOINC

  • 31208-2
  • 75325-1
  • 35462-1
  • 54449-4
  • 82155-3
  • 49857-6

LDT or Modified FDA

Yes

Available Stat

No

Ordering Recommendations

Use to confirm a suspected diagnosis of spinal muscular atrophy (SMA) and quantify SMN2 copy number for treatment purposes in affected individuals. Use for prenatal or preconception carrier screening for SMA in the general population, carrier screening for the reproductive partner of a known SMA carrier, and carrier screening for parents of a child with a deletion of the SMN1 gene or other family history of SMA.

Test Code

UCSF Test Code LAB4259

ARUP Test Code

2013436

Performing Lab

ARUP

Sendout

Yes, ARUP

Performed

Varies

Methodology

Multiplex Ligation-Dependent Probe Amplification (MLPA)

Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B)

Sample Type

EDTA whole blood

Specimen Preparation

Transport 2 mL whole blood. (Min: 1 mL)

Reference Interval

By report

Interpretive Data

Refer to report.

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy
  • SMA
  • SMN1
  • SMN2
  • Spinal Muscular Atrophy

Storage/Transport Temperature

Refrigerated. Also acceptable: Ambient.

Stability (from collection to initiation)

Room Temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Reported

7-14 days

Additional Information

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier rate of about 1 in 50 in the US, leading to disease in approximately 1 in 10,000 live births. SMA is a neuromuscular disorder and a frequently inherited cause of infant mortality. SMA is characterized by degeneration of lower motor neurons in the spinal cord and brain stem, leading to muscle wasting and paralysis. The disorder is classified into four subtypes (I-IV) based on the age of onset, which can range from infancy to adulthood. In its most severe form (Type I), SMA leads to death in infancy. In other non-fatal forms, affected individuals become disabled. Treatment in these cases is aimed at slow progression of the disease. 

SMN1 Copy Number Assay
SMA is most often caused by deletions in theSMN1 gene and thus molecular testing assesses the number of copies of SMN1. Individuals affected with SMA have 0 copies of the SMN1 gene, whereas individuals with 1 copy of the SMN1 gene are predicted to be carriers of SMA. Individuals with 2 or more copies have a reduced risk to be carriers, namely because individuals, who are carriers of SMA as a result of either 2 or 3 copies of SMN1 on one chromosome and the absence of SMN1 on the other chromosome (termed as 2+0 or 3+0) cannot be detected by this assay. The 2+0 genotype occurs in about 3-4% of the general population. This assay will determine SMN1 copy number, but will not detect intragenic mutations within theSMN1gene.

SMN1 Linked Variants Assay
Duplication of SMN1 has been linked to a haplotype that spans two linked variants (rs143838139 and rs200800214). The presence of these two variants, especially in Ashkenazi Jews and Asians, increases the likelihood of a 2+0 SMN1 genotype, but does not confirm it. This assay will also determine the presence or absence of these two linked variants. Carrier risks estimation based on SMN1 copy number analysis and detection of the linked variants is shown in the Table below.

SMN2 Copy Number Assay
SMN2 is adjacent to SMN1 on chromosome 5 and differs from it by only a few bases. However, SMN2 expresses only about 10% of functional mRNA due to a defect in RNA splicing. Individuals can carry multiple copy numbers of SMN2, ranging from 0 to 5 copies per chromosome. Thus, the presence of multiple copy numbers of SMN2 with 0 copy SMN1 is associated with reduced severity of SMA, thereby accounting for the various SMA phenotypic subtypes. This assay will also determine SMN2 copy number.
 
Ethnic
Group		 Prior Risk CN
Detect. Rate		 CN3
Res. Risk		 CN2+NEG LV
Res. Risk		 CN2+POS LV
Res. Risk
Caucasian 1 in 35 95% 1 in 3,500 1 in 769 1 in 29
Ashkenazi Jewish 1 in 41 90% 1 in 4,000 1 in 580 Likely Carrier
Asian 1 in 53 93% 1 in 5,000 1 in 702 Likely Carrier
African American 1 in 66 71% 1 in 3,000 1 in 396 1 in 34
Hispanic 1 in 117 91% 1 in 11,000 1 in 1762 1 in 140
 
  1. Hendrickson BC et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641–644, 2009
  2. Ogino S et al. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet; 110:301-317, 2002
  3. Prior TW et al. Technical standards and guidelines for spinal muscular atrophy testing. Genet in Med. 13:686-694, 2011
  4. Luo M et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-156, 2013
  5. Sugarman EA et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 27-32, 2012
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.

Additional Technical Information

CPT Codes

81329

LOINC

  • 31208-2
  • 75325-1
  • 35462-1
  • 54449-4
  • 82155-3
  • 49857-6

LDT or Modified FDA

Yes
Ordering

Ordering Recommendations

Use to confirm a suspected diagnosis of spinal muscular atrophy (SMA) and quantify SMN2 copy number for treatment purposes in affected individuals. Use for prenatal or preconception carrier screening for SMA in the general population, carrier screening for the reproductive partner of a known SMA carrier, and carrier screening for parents of a child with a deletion of the SMN1 gene or other family history of SMA.

Available Stat

No

Performing Lab

ARUP

Performed

Varies

Methodology

Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reported

7-14 days

Additional Technical Information

Additional Information

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier rate of about 1 in 50 in the US, leading to disease in approximately 1 in 10,000 live births. SMA is a neuromuscular disorder and a frequently inherited cause of infant mortality. SMA is characterized by degeneration of lower motor neurons in the spinal cord and brain stem, leading to muscle wasting and paralysis. The disorder is classified into four subtypes (I-IV) based on the age of onset, which can range from infancy to adulthood. In its most severe form (Type I), SMA leads to death in infancy. In other non-fatal forms, affected individuals become disabled. Treatment in these cases is aimed at slow progression of the disease. 

SMN1 Copy Number Assay
SMA is most often caused by deletions in theSMN1 gene and thus molecular testing assesses the number of copies of SMN1. Individuals affected with SMA have 0 copies of the SMN1 gene, whereas individuals with 1 copy of the SMN1 gene are predicted to be carriers of SMA. Individuals with 2 or more copies have a reduced risk to be carriers, namely because individuals, who are carriers of SMA as a result of either 2 or 3 copies of SMN1 on one chromosome and the absence of SMN1 on the other chromosome (termed as 2+0 or 3+0) cannot be detected by this assay. The 2+0 genotype occurs in about 3-4% of the general population. This assay will determine SMN1 copy number, but will not detect intragenic mutations within theSMN1gene.

SMN1 Linked Variants Assay
Duplication of SMN1 has been linked to a haplotype that spans two linked variants (rs143838139 and rs200800214). The presence of these two variants, especially in Ashkenazi Jews and Asians, increases the likelihood of a 2+0 SMN1 genotype, but does not confirm it. This assay will also determine the presence or absence of these two linked variants. Carrier risks estimation based on SMN1 copy number analysis and detection of the linked variants is shown in the Table below.

SMN2 Copy Number Assay
SMN2 is adjacent to SMN1 on chromosome 5 and differs from it by only a few bases. However, SMN2 expresses only about 10% of functional mRNA due to a defect in RNA splicing. Individuals can carry multiple copy numbers of SMN2, ranging from 0 to 5 copies per chromosome. Thus, the presence of multiple copy numbers of SMN2 with 0 copy SMN1 is associated with reduced severity of SMA, thereby accounting for the various SMA phenotypic subtypes. This assay will also determine SMN2 copy number.
 
Ethnic
Group		 Prior Risk CN
Detect. Rate		 CN3
Res. Risk		 CN2+NEG LV
Res. Risk		 CN2+POS LV
Res. Risk
Caucasian 1 in 35 95% 1 in 3,500 1 in 769 1 in 29
Ashkenazi Jewish 1 in 41 90% 1 in 4,000 1 in 580 Likely Carrier
Asian 1 in 53 93% 1 in 5,000 1 in 702 Likely Carrier
African American 1 in 66 71% 1 in 3,000 1 in 396 1 in 34
Hispanic 1 in 117 91% 1 in 11,000 1 in 1762 1 in 140
 
  1. Hendrickson BC et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641–644, 2009
  2. Ogino S et al. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet; 110:301-317, 2002
  3. Prior TW et al. Technical standards and guidelines for spinal muscular atrophy testing. Genet in Med. 13:686-694, 2011
  4. Luo M et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-156, 2013
  5. Sugarman EA et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 27-32, 2012
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy
  • SMA
  • SMN1
  • SMN2
  • Spinal Muscular Atrophy
Collection

Sample Type

EDTA whole blood

Label Abbreviation

SMA

Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B)

Stability (from collection to initiation)

Room Temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Storage/Transport Temperature

Refrigerated. Also acceptable: Ambient.
Processing

Test Code

UCSF Test Code LAB4259

ARUP Test Code

2013436

Sendout

Yes, ARUP

Performing Lab

ARUP

Specimen Preparation

Transport 2 mL whole blood. (Min: 1 mL)

Stability (from collection to initiation)

Room Temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Storage/Transport Temperature

Refrigerated. Also acceptable: Ambient.
Result Interpretation

Reference Interval

By report

Additional Information

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier rate of about 1 in 50 in the US, leading to disease in approximately 1 in 10,000 live births. SMA is a neuromuscular disorder and a frequently inherited cause of infant mortality. SMA is characterized by degeneration of lower motor neurons in the spinal cord and brain stem, leading to muscle wasting and paralysis. The disorder is classified into four subtypes (I-IV) based on the age of onset, which can range from infancy to adulthood. In its most severe form (Type I), SMA leads to death in infancy. In other non-fatal forms, affected individuals become disabled. Treatment in these cases is aimed at slow progression of the disease. 

SMN1 Copy Number Assay
SMA is most often caused by deletions in theSMN1 gene and thus molecular testing assesses the number of copies of SMN1. Individuals affected with SMA have 0 copies of the SMN1 gene, whereas individuals with 1 copy of the SMN1 gene are predicted to be carriers of SMA. Individuals with 2 or more copies have a reduced risk to be carriers, namely because individuals, who are carriers of SMA as a result of either 2 or 3 copies of SMN1 on one chromosome and the absence of SMN1 on the other chromosome (termed as 2+0 or 3+0) cannot be detected by this assay. The 2+0 genotype occurs in about 3-4% of the general population. This assay will determine SMN1 copy number, but will not detect intragenic mutations within theSMN1gene.

SMN1 Linked Variants Assay
Duplication of SMN1 has been linked to a haplotype that spans two linked variants (rs143838139 and rs200800214). The presence of these two variants, especially in Ashkenazi Jews and Asians, increases the likelihood of a 2+0 SMN1 genotype, but does not confirm it. This assay will also determine the presence or absence of these two linked variants. Carrier risks estimation based on SMN1 copy number analysis and detection of the linked variants is shown in the Table below.

SMN2 Copy Number Assay
SMN2 is adjacent to SMN1 on chromosome 5 and differs from it by only a few bases. However, SMN2 expresses only about 10% of functional mRNA due to a defect in RNA splicing. Individuals can carry multiple copy numbers of SMN2, ranging from 0 to 5 copies per chromosome. Thus, the presence of multiple copy numbers of SMN2 with 0 copy SMN1 is associated with reduced severity of SMA, thereby accounting for the various SMA phenotypic subtypes. This assay will also determine SMN2 copy number.
 
Ethnic
Group		 Prior Risk CN
Detect. Rate		 CN3
Res. Risk		 CN2+NEG LV
Res. Risk		 CN2+POS LV
Res. Risk
Caucasian 1 in 35 95% 1 in 3,500 1 in 769 1 in 29
Ashkenazi Jewish 1 in 41 90% 1 in 4,000 1 in 580 Likely Carrier
Asian 1 in 53 93% 1 in 5,000 1 in 702 Likely Carrier
African American 1 in 66 71% 1 in 3,000 1 in 396 1 in 34
Hispanic 1 in 117 91% 1 in 11,000 1 in 1762 1 in 140
 
  1. Hendrickson BC et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641–644, 2009
  2. Ogino S et al. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet; 110:301-317, 2002
  3. Prior TW et al. Technical standards and guidelines for spinal muscular atrophy testing. Genet in Med. 13:686-694, 2011
  4. Luo M et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-156, 2013
  5. Sugarman EA et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 27-32, 2012
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.

Additional Technical Information

Interpretive Data

Refer to report.

Administrative

CPT Codes

81329

LOINC

  • 31208-2
  • 75325-1
  • 35462-1
  • 54449-4
  • 82155-3
  • 49857-6

LDT or Modified FDA

Yes
Complete View

Available Stat

No

Ordering Recommendations

Use to confirm a suspected diagnosis of spinal muscular atrophy (SMA) and quantify SMN2 copy number for treatment purposes in affected individuals. Use for prenatal or preconception carrier screening for SMA in the general population, carrier screening for the reproductive partner of a known SMA carrier, and carrier screening for parents of a child with a deletion of the SMN1 gene or other family history of SMA.

Test Code

UCSF Test Code LAB4259

ARUP Test Code

2013436

Performing Lab

ARUP

Sendout

Yes, ARUP

Performed

Varies

Methodology

Multiplex Ligation-Dependent Probe Amplification (MLPA)

Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B)

Sample Type

EDTA whole blood

Specimen Preparation

Transport 2 mL whole blood. (Min: 1 mL)

Reference Interval

By report

Interpretive Data

Refer to report.

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy
  • SMA
  • SMN1
  • SMN2
  • Spinal Muscular Atrophy

Storage/Transport Temperature

Refrigerated. Also acceptable: Ambient.

Stability (from collection to initiation)

Room Temperature: 1 week; Refrigerated: 1 month; Frozen: Unacceptable.

Reported

7-14 days

Additional Information

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier rate of about 1 in 50 in the US, leading to disease in approximately 1 in 10,000 live births. SMA is a neuromuscular disorder and a frequently inherited cause of infant mortality. SMA is characterized by degeneration of lower motor neurons in the spinal cord and brain stem, leading to muscle wasting and paralysis. The disorder is classified into four subtypes (I-IV) based on the age of onset, which can range from infancy to adulthood. In its most severe form (Type I), SMA leads to death in infancy. In other non-fatal forms, affected individuals become disabled. Treatment in these cases is aimed at slow progression of the disease. 

SMN1 Copy Number Assay
SMA is most often caused by deletions in theSMN1 gene and thus molecular testing assesses the number of copies of SMN1. Individuals affected with SMA have 0 copies of the SMN1 gene, whereas individuals with 1 copy of the SMN1 gene are predicted to be carriers of SMA. Individuals with 2 or more copies have a reduced risk to be carriers, namely because individuals, who are carriers of SMA as a result of either 2 or 3 copies of SMN1 on one chromosome and the absence of SMN1 on the other chromosome (termed as 2+0 or 3+0) cannot be detected by this assay. The 2+0 genotype occurs in about 3-4% of the general population. This assay will determine SMN1 copy number, but will not detect intragenic mutations within theSMN1gene.

SMN1 Linked Variants Assay
Duplication of SMN1 has been linked to a haplotype that spans two linked variants (rs143838139 and rs200800214). The presence of these two variants, especially in Ashkenazi Jews and Asians, increases the likelihood of a 2+0 SMN1 genotype, but does not confirm it. This assay will also determine the presence or absence of these two linked variants. Carrier risks estimation based on SMN1 copy number analysis and detection of the linked variants is shown in the Table below.

SMN2 Copy Number Assay
SMN2 is adjacent to SMN1 on chromosome 5 and differs from it by only a few bases. However, SMN2 expresses only about 10% of functional mRNA due to a defect in RNA splicing. Individuals can carry multiple copy numbers of SMN2, ranging from 0 to 5 copies per chromosome. Thus, the presence of multiple copy numbers of SMN2 with 0 copy SMN1 is associated with reduced severity of SMA, thereby accounting for the various SMA phenotypic subtypes. This assay will also determine SMN2 copy number.
 
Ethnic
Group		 Prior Risk CN
Detect. Rate		 CN3
Res. Risk		 CN2+NEG LV
Res. Risk		 CN2+POS LV
Res. Risk
Caucasian 1 in 35 95% 1 in 3,500 1 in 769 1 in 29
Ashkenazi Jewish 1 in 41 90% 1 in 4,000 1 in 580 Likely Carrier
Asian 1 in 53 93% 1 in 5,000 1 in 702 Likely Carrier
African American 1 in 66 71% 1 in 3,000 1 in 396 1 in 34
Hispanic 1 in 117 91% 1 in 11,000 1 in 1762 1 in 140
 
  1. Hendrickson BC et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641–644, 2009
  2. Ogino S et al. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet; 110:301-317, 2002
  3. Prior TW et al. Technical standards and guidelines for spinal muscular atrophy testing. Genet in Med. 13:686-694, 2011
  4. Luo M et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-156, 2013
  5. Sugarman EA et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 27-32, 2012
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.

Additional Technical Information

CPT Codes

81329

LOINC

  • 31208-2
  • 75325-1
  • 35462-1
  • 54449-4
  • 82155-3
  • 49857-6

LDT or Modified FDA

Yes

ARUP Consult®

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