Available Stat

No

Performing Lab

Medical Genomics - Molecular Diagnostics

Performed

Run 1-2x per week, and as needed.

Methodology

Real time PCR for copy number analysis and allele-specific probes hybridization for linked variants detection.

Reported

14-21 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.

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy

Sample Type

EDTA whole blood
Amniotic fluid
Cultured amniocytes
Chorionic villi
Cultured chorionic villi

Collect

Lavender top

Amount to Collect

See preferred volume.

Preferred Volume

Blood 5 ml
Amniotic fluid 20 ml
Cultured amniocytes 2 T25 flasks
Chorionic villi 20 mg
Cultured chorionic villi 2 T25 flasks

Minimum Volume

Blood 2 ml
Amniotic fluid 10 ml
Cultured amniocytes 1 T25 flasks
Chorionic villi 10 mg
Cultured chorionic villi: 1 T25 flask

Remarks

Do not collect sample in heparin. Keep sample refrigerated for overnight or longer storage.

Unacceptable Conditions

Heparinized samples. Low confluence cultures. Insufficient amount of amniotic fluid or chorionic villi

Test Code

SMAPCR

Performing Lab

Medical Genomics - Molecular Diagnostics

Specimen Preparation

Refrigerate sample. DO NOT centrifuge or freeze.

Preferred Volume

Blood 5 ml
Amniotic fluid 20 ml
Cultured amniocytes 2 T25 flasks
Chorionic villi 20 mg
Cultured chorionic villi 2 T25 flasks

Minimum Volume

Blood 2 ml
Amniotic fluid 10 ml
Cultured amniocytes 1 T25 flasks
Chorionic villi 10 mg
Cultured chorionic villi: 1 T25 flask

Unacceptable Conditions

Heparinized samples. Low confluence cultures. Insufficient amount of amniotic fluid or chorionic villi

Reference Interval

SMN1: 2 copies 
SMN2: 2 copies
SMN1 c.*3+80T>G (rs143838139) - Not detected
SMN1 c.*211_*212del(rs200800214) - Not detected
 

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.

CPT Codes

81329, 81337

LDT or Modified FDA

Yes

Available Stat

No

Test Code

SMAPCR

Performing Lab

Medical Genomics - Molecular Diagnostics

Performed

Run 1-2x per week, and as needed.

Methodology

Real time PCR for copy number analysis and allele-specific probes hybridization for linked variants detection.

Remarks

Do not collect sample in heparin. Keep sample refrigerated for overnight or longer storage.

Collect

Lavender top

Amount to Collect

See preferred volume.

Sample Type

EDTA whole blood
Amniotic fluid
Cultured amniocytes
Chorionic villi
Cultured chorionic villi

Preferred Volume

Blood 5 ml
Amniotic fluid 20 ml
Cultured amniocytes 2 T25 flasks
Chorionic villi 20 mg
Cultured chorionic villi 2 T25 flasks

Minimum Volume

Blood 2 ml
Amniotic fluid 10 ml
Cultured amniocytes 1 T25 flasks
Chorionic villi 10 mg
Cultured chorionic villi: 1 T25 flask

Unacceptable Conditions

Heparinized samples. Low confluence cultures. Insufficient amount of amniotic fluid or chorionic villi

Specimen Preparation

Refrigerate sample. DO NOT centrifuge or freeze.

Reference Interval

SMN1: 2 copies 
SMN2: 2 copies
SMN1 c.*3+80T>G (rs143838139) - Not detected
SMN1 c.*211_*212del(rs200800214) - Not detected
 

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy

Reported

14-21 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.

CPT Codes

81329, 81337

LDT or Modified FDA

Yes
Ordering

Available Stat

No

Performing Lab

Medical Genomics - Molecular Diagnostics

Performed

Run 1-2x per week, and as needed.

Methodology

Real time PCR for copy number analysis and allele-specific probes hybridization for linked variants detection.

Reported

14-21 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.

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy
Collection

Sample Type

EDTA whole blood
Amniotic fluid
Cultured amniocytes
Chorionic villi
Cultured chorionic villi

Collect

Lavender top

Amount to Collect

See preferred volume.

Preferred Volume

Blood 5 ml
Amniotic fluid 20 ml
Cultured amniocytes 2 T25 flasks
Chorionic villi 20 mg
Cultured chorionic villi 2 T25 flasks

Minimum Volume

Blood 2 ml
Amniotic fluid 10 ml
Cultured amniocytes 1 T25 flasks
Chorionic villi 10 mg
Cultured chorionic villi: 1 T25 flask

Remarks

Do not collect sample in heparin. Keep sample refrigerated for overnight or longer storage.

Unacceptable Conditions

Heparinized samples. Low confluence cultures. Insufficient amount of amniotic fluid or chorionic villi
Processing

Test Code

SMAPCR

Performing Lab

Medical Genomics - Molecular Diagnostics

Specimen Preparation

Refrigerate sample. DO NOT centrifuge or freeze.

Preferred Volume

Blood 5 ml
Amniotic fluid 20 ml
Cultured amniocytes 2 T25 flasks
Chorionic villi 20 mg
Cultured chorionic villi 2 T25 flasks

Minimum Volume

Blood 2 ml
Amniotic fluid 10 ml
Cultured amniocytes 1 T25 flasks
Chorionic villi 10 mg
Cultured chorionic villi: 1 T25 flask

Unacceptable Conditions

Heparinized samples. Low confluence cultures. Insufficient amount of amniotic fluid or chorionic villi
Result Interpretation

Reference Interval

SMN1: 2 copies 
SMN2: 2 copies
SMN1 c.*3+80T>G (rs143838139) - Not detected
SMN1 c.*211_*212del(rs200800214) - Not detected
 

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.
Administrative

CPT Codes

81329, 81337

LDT or Modified FDA

Yes
Complete View

Available Stat

No

Test Code

SMAPCR

Performing Lab

Medical Genomics - Molecular Diagnostics

Performed

Run 1-2x per week, and as needed.

Methodology

Real time PCR for copy number analysis and allele-specific probes hybridization for linked variants detection.

Remarks

Do not collect sample in heparin. Keep sample refrigerated for overnight or longer storage.

Collect

Lavender top

Amount to Collect

See preferred volume.

Sample Type

EDTA whole blood
Amniotic fluid
Cultured amniocytes
Chorionic villi
Cultured chorionic villi

Preferred Volume

Blood 5 ml
Amniotic fluid 20 ml
Cultured amniocytes 2 T25 flasks
Chorionic villi 20 mg
Cultured chorionic villi 2 T25 flasks

Minimum Volume

Blood 2 ml
Amniotic fluid 10 ml
Cultured amniocytes 1 T25 flasks
Chorionic villi 10 mg
Cultured chorionic villi: 1 T25 flask

Unacceptable Conditions

Heparinized samples. Low confluence cultures. Insufficient amount of amniotic fluid or chorionic villi

Specimen Preparation

Refrigerate sample. DO NOT centrifuge or freeze.

Reference Interval

SMN1: 2 copies 
SMN2: 2 copies
SMN1 c.*3+80T>G (rs143838139) - Not detected
SMN1 c.*211_*212del(rs200800214) - Not detected
 

Synonyms

  • Werdnig-Hoffmann disease
  • SMA type I, II, III, IV
  • Congenital axonal neuropathy

Reported

14-21 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.

CPT Codes

81329, 81337

LDT or Modified FDA

Yes

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