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P060 SMA Carrier

SALSA® MLPA® Probemix P060 SMA Carrier detects copy number variations in exons 7 and 8 of the SMN1 gene. P060 SMA has been specifically designed for SMA carrier detection.

Specifications

Contents: 21 MLPA probes, including 2 probes for SMN1 (exon 7 and 8), 2 probes for SMN2 (exon 7 and 8) and 17 reference probes.

Tissue: genomic DNA isolated from human peripheral whole blood

Application: spinal muscular atrophy (SMA).

IVDR certified and registered for in vitro diagnostic (IVD) use in selected territories.

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List Prices Documentation

Key related products

P021 SMA

Spinal muscular atrophy (SMA). Determine SMN1 and SMN2 copy number; best suited for patient detection.

P460 SMA (Silent) Carrier

Spinal muscular atrophy (SMA). Determine SMN1 copy number and an increased risk for the 2+0 carrier genotype by detection of two associated polymorphisms (g.27134T>G and g.27706-27707delAT).

MC002 SMA Newborn Screen

Spinal muscular atrophy (SMA). Newborn screening for homozygous deletions of exon 7 of SMN1.

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This product has recently been CE-marked for in vitro diagnostic (IVD) use under the In Vitro Diagnostic Regulation (IVDR; EU 2017/746), which replaces the former CE-marking under the IVD Directive (IVDD; Directive 98/79/EC). This update was accompanied by a change in the intended purpose and a change in format of the product description. Some information can now be found in a different location (more information).

MRC Holland offers four different assays for SMA that fit the complete range of genetic testing needs. Compare our SMA products.

Intended purpose

The SALSA MLPA Probemix P060 SMA Carrier is an in vitro diagnostic (IVD) or research use only (RUO) manual semi-quantitative assay for the detection of deletions or duplication in exons 7 and 8 of the SMN1 gene in genomic DNA isolated from human peripheral whole blood specimens. P060 SMA Carrier is intended to establish or confirm a potential cause for and clinical diagnosis of Spinal Muscular Atrophy (SMA), carrier testing and for molecular genetic testing of at-risk family members. This probemix can also be used for the detection of copy number changes of exons 7 and 8 of the SMN2 gene, as an interpretation aid for SMN1 copy number determination.

For the full intended purpose, see the product description.

Clinical background

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. The estimated incidence of SMA is 1:6,000-1:10,000: the second most common lethal autosomal recessive disorder in Caucasians, after cystic fibrosis (Ben-Shachar et al. 2011, Smith et al. 2007). SMA is usually divided into four clinical groups based on age of onset and maximum function obtained.

Two (highly similar) genes play a pivotal role in SMA: SMN1 and SMN2. Most individuals* have two copies of each gene. The SMA region on 5q13.2, containing the telomeric SMN1 and the centromeric SMN2, is a complicated inverted repeat area displaying high instability, leading to frequent deletions and gene conversions. SMN1 and SMN2 can only be distinguished by two single nucleotide differences: one in exon 7 and one in exon 8. The single nucleotide difference between SMN1 and SMN2 in exon 7 affects mRNA splicing in SMN2 resulting in an altered SMN protein with a limited half-life and function.

A total of 95-98% of SMA patients (this percentage is lower in SMA patients from African descent) show homozygous deletion of at least exon 7 of the telomeric SMN1 gene (Labrum et al. 2007). The remaining 3-5% present compound heterozygosity with a point mutation on one chromosome and a deletion/gene conversion on the other. Such a point mutation will not be detected by this P060 SMA Carrier MLPA assay and should be identified by sequencing. In a small number of patients, the SMN1 defect is a copy number change of SMN1 exons 1-6 which can be detected with the SALSA MLPA Probemix P021 SMA (Arkblad et al. 2006).

The great majority of SMA carriers can be identified by the presence of a single SMN1 exon 7 copy. The one copy frequency in the US is estimated to be 1:37 for Caucasians, 1:46 for Ashkenazi Jews, 1:56 for Asians, 1:91 for African-Americans and 1:125 for Hispanics. Approximately 3-8% of SMA carriers (27% of African Americans) have one functional and one defective SMN1 copy, or have two SMN1 copies on one chromosome and 0 copies on the other (2+0) (Alias et al. 2014, Ben-Shachar et al. 2011, Hendrickson et al. 2009, Miskovic et al. 2011, Smith et al. 2007). Dosage analysis cannot determine the difference between '1+1' and '2+0' (silent carriers) arrangements. Both situations are simply detected as having two SMN1 copies leading to false negative results. A thorough molecular analysis should be performed in parents of SMA patients who have two SMN1 copies. Luo et al. (2014) reported that a haplotype block specific for SMN1 duplications is present in a large percentage of Ashkenazi Jews and in other ethnic groups. Identifying this haplotype, e.g. with the use of the SALSA MLPA Probemix P460 SMA (Silent) Carrier, will, depending on ethnicity, increase the chance of identifying silent carriers.

The SMN2 copy number is very variable with only 60-70% of individuals having two copies. Provided that at least one functional SMN1 copy is present, complete absence of the centromeric SMN2 gene has no known clinical consequences. More information on spinal muscular atrophy can be found in http://www.ncbi.nlm.nih.gov/books/NBK1352/.

*In people of African descent, the percentage of SMA patients with a homozygous exon 7 deletion may be lower (Labrum et al. 2007). This assay does not detect other causes of SMA such as pathogenic point mutations.

Regulatory status

SALSA MLPA Probemix P060 SMA Carrier is CE-marked under the IVDR for in vitro diagnostic (IVD) use in Europe. This assay has also been registered for IVD use in Colombia, Costa Rica and Israel.

This assay is for research use only (RUO) in all other territories.

SALSA Sample DNA for this product

SALSA Reference Selection DNA SD082 can be used to aid in the selection of suitable reference samples for the P060 SMA Carrier probemix. Reference Selection DNA can only be used in initial experiments on DNA samples from healthy individuals from your sample collection with the intention to identify suitable reference samples. SD082 cannot be used as a reference sample in subsequent experiments.

A vial of SALSA Reference Selection DNA SD082 is included with every order of the P060 SMA Carrier probemix, but it is possible to order additional vials separately.

For more information, see the product description.

Product documentation

Version B2

Other versions

Contact us for earlier versions.

Translations and Summary of Safety and Performance

Translations of the product description in selected European languages are available upon request. Please contact us or one of our local sales partners. Translations of the MLPA General Protocol in selected languages are available here.

The Summary of Safety and Performance (SSP) is also available upon request.

List prices

Product

Item no.
Description
Technology
Price
P060-025R
SALSA MLPA Probemix P060 SMA Carrier – 25 rxn
MLPA
€ 286.00
P060-050R
SALSA MLPA Probemix P060 SMA Carrier – 50 rxn
MLPA
€ 560.00
P060-100R
SALSA MLPA Probemix P060 SMA Carrier – 100 rxn
MLPA
€ 1096.00

Required reagents

A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM (6 vials)
MLPA MS-MLPA
€ 348.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
MLPA MS-MLPA
€ 348.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 1600.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
MLPA MS-MLPA
€ 1600.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 6152.00

Sample DNAs (included)

A vial is included with every order of this probemix, but additional vials can also be purchased separately.

Item no.
Description
Technology
Price
SD082
SALSA Reference Selection DNA SD082 – 6 rxn
MLPA
€ 24.15

Price details & ordering

The prices above are list prices for direct orders from MRC Holland. Contact us for a quote that takes discounts and additional costs (such as shipping costs) into account. Different prices apply for orders through one of our sales partners; contact your local supplier for a quote.

More information about ordering & prices

Positive samples

Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.

The commercially available positive samples below have been tested with the current (B2) version of this product and have been shown to produce useful results.

Coriell Sample ID Copy Number
SMN1 exon 7 SMN2 exon 7 SMN1 exon 8 SMN2 exon 8
NA00232; NA106840202
NA22592; NA09677; NA038130303
NA03815; NA20760; NA207871111
NA23687; NA23688; NA207641212
HG00346; HG002811313
HG01773; HG01774; HG0213214*14*
NA19122; HG01941; NA197942020
HG02514; HG03663; HG036362121
HG01701; HG01942; HG019352222
HG01748; HG01971; HG003292323
HG0362524*24*
NA19123; HG03258; HG02891; HG00255; NA19437; HG013773030
HG01755; HG03650; NA20775; HG011373131
NA12548; NA207553232
NA12552; NA205153333
NA19235; HG03027; HG027694040
NA19429; HG028364141

Samples with a different copy number for exon 7 and 8 due to gene conversion

Coriell Sample ID Copy Number
SMN1 exon 7 SMN2 exon 7 SMN1 exon 8 SMN2 exon 8
NA191772130
NA215272213
NA192492231
NA215262314*
NA197903113
NA193273122
NA215133140
NA193604031
HG026974132

* SMN2 probes in this probemix cannot reliably distinguish between 4 or more copies. The indicated copy numbers have been validated using SALSA MLPA Probemix P021 SMA.

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P060 SMA Carrier

  • Cao Y et al. (2020). Transmission characteristics of SMN from 227 spinal muscular atrophy core families in China. J Hum Genet. 65:469-73.
  • Davidson JE et al. (2023). The Carrier Frequency of Two SMN1 Genes in Parents of Symptomatic Children with SMA and the Significance of SMN1 Exon 8 in Carriers. Genes (Basel). 14:1403.
  • Lin Y et al. (2019). Newborn Screening for Spinal Muscular Atrophy in China Using DNA Mass Spectrometry. Front Genet. 10:1255.
  • Miskovic M et al. (2011). Lower incidence of deletions in the survival of motor neuron gene and the neuronal apoptosis inhibitory protein gene in children with spinal muscular atrophy from Serbia. Tohoku J Exp Med. 225:153-9.
  • Sun Y et al. (2020). Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China. BMC Med Genet. 21:133.
  • Zhao S et al. (2022). Next generation sequencing is a highly reliable method to analyze exon 7 deletion of survival motor neuron 1 (SMN1) gene. Sci Rep. 12:223.

Selected publications using SALSA MLPA Probemix P060 SMA Carrier and P021 SMA

  • Cheung VCK et al. (2024). Motor patterns of patients with spinal muscular atrophy suggestive of sensory and corticospinal contributions to the development of locomotor muscle synergies. J Neurophysiol. 131:338-59.
  • Jiang Y et al. (2024). Development of a low-cost and accurate carrier screening method for spinal muscular atrophy in developing countries. Eur J Med Genet. 68:104921.
  • Laurito S et al. (2018). The impact of paralog genes: detection of copy number variation in spinal muscle atrophy patients. Biocell. 42:87-92.
  • Qu Y et al. (2024). Variants located in intron 6 of SMN1 lead to misdiagnosis in genetic detection and screening for SMA. Heliyon. 10:e28015.
  • Ricci M et al. (2023). Clinical Phenotype of Pediatric and Adult Patients With Spinal Muscular Atrophy With Four SMN2 Copies: Are They Really All Stable? Ann Neurol. 94:1126-35.

References

  • Alías L et al. (2014). Improving detection and genetic counseling in carriers of spinal muscular atrophy with two copies of the SMN1 gene. Clin Genet. 85:470-5.
  • Arkblad EL et al. (2006). Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy. Neuromuscul Disord. 16:830-8.
  • Ben-Shachar S et al. (2011). Large-scale population screening for spinal muscular atrophy: clinical implications. Genet Med. 13:110-4.
  • Hendrickson BC et al. (2009). Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641-4.
  • Labrum R et al. (2007). The molecular basis of spinal muscular atrophy (SMA) in South African black patients. Neuromuscul Disord. 17:684-92.
  • Luo M et al. (2014). An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 16:149-56.
  • Miskovic M et al. (2011). Lower incidence of deletions in the survival of motor neuron gene and the neuronal apoptosis inhibitory protein gene in children with spinal muscular atrophy from Serbia. Tohoku J Exp Med. 225:153-9.
  • Smith M et al. (2007). Population screening and cascade testing for carriers of SMA. Eur J Hum Genet. 15:759-66.
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CE

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

CE2797

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

CO

IVD-registered in Colombia.

CR

IVD-registered in Costa Rica.

IL

IVD-registered in Israel.