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P460 SMA (Silent) Carrier

SALSA® MLPA® Probemix P460 SMA (Silent) Carrier detects copy number variations in the SMN1 and SMN2 genes. P460 SMA has been specifically designed for SMA carrier detection and risk factors for silent carriers.

Specifications

Contents: 23 MLPA probes, including 2 probes for SMN1, 1 probe for SMN1 polymorphisms g.27134T>G and g.27706-27707delAT each, and 1 probe for SMN2.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: spinal muscular atrophy (SMA).

IVDD certified for in vitro diagnostic (IVD) use.

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Key related products

P060 SMA Carrier

Spinal muscular atrophy (SMA). Determine SMN1 and SMN2 copy number; best suited for carrier testing/screening.

P021 SMA

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

MC002 SMA Newborn Screen

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

View all

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 P460 SMA (Silent) Carrier is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative assay for the detection of 1. copy number changes of exons 7 and 8 of the SMN1 gene for carrier testing, patient diagnosis and for the confirmation of a potential cause and clinical diagnosis of spinal muscular atrophy (SMA), and 2. the presence of the g.27134T>G and g.27706-27707delAT polymorphisms in SMN1 that are a risk factor for silent carriership of SMA in genomic DNA isolated from human peripheral whole blood specimens. P460 SMA (Silent) Carrier is also intended for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

Clinical background

The SALSA MLPA Probemix P460 SMA (Silent) Carrier is an assay for the detection of deletions or duplications in the SMN1 gene, which are associated with Spinal Muscular Atrophy (SMA). This probemix can also be used to detect the presence of two SMN1 polymorphisms, g.27134T>G and g.27706-27707delAT, for haplotype identification.

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. SMA is the second most common lethal autosomal recessive disorder in Caucasians, after cystic fibrosis. SMA is usually divided into three clinical groups. Patients with type I SMA (OMIM# 253300) show onset at birth or before six months, and usually die of respiratory insufficiency within two years. Type I SMA patients are never able to sit or walk. Patients with type II SMA (OMIM# 253550) show onset after six months. They can sit but are never able to walk unaided, and their life expectancy is significantly reduced. Type III SMA (OMIM# 253400) patients show the first symptoms after 18 months and are able to stand and walk, but often become wheelchair-bound during youth or adulthood.

There are two (highly similar) genes playing a pivotal role in SMA: SMN1 and SMN2. The telomeric SMN1 and the centromeric SMN2 genes are located in a complicated inverted repeat area spanning ~500 kb on chromosome 5q13.2. This area displays high instability, leading to frequent deletions and gene conversions. Most individuals have two copies each of SMN1 and SMN2, both consisting of nine exons (exons 1, 2a, 2b, and 3-8). The SMN1 and SMN2 genes can only be distinguished by two single nucleotide differences: one in exon 7 and one in exon 8. The exon 8 difference has no effect on the transcript; however, the exon 7 difference disrupts splicing in SMN2 most of the time leading to loss of functionality. Only 10-15% of the SMN2 transcripts are functional. This SALSA MLPA Probemix P460 SMA (Silent) Carrier detects the copy number of exons 7 and 8 of the SMN1 gene.

Absence of any functional SMN1 copy results in insufficient amounts of full-length transcripts. More than 95% of SMA patients show homozygous deletion of at least exon 7 of the telomeric SMN1 gene. Individuals with only one functional SMN1 copy are carriers of the disease. The great majority of SMA carriers can be identified by the presence of only 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 (Hendrickson et al. 2009).

Although the great majority of SMA carriers can be detected by copy number analysis of the SMN1 exon 7 sequence, some carriers remain undetected. These include carriers with (1) a defective SMN1 allele due to a point mutation in the SMN1 gene or a copy number change of exons 1-6 or 8, and (2) individuals that have two SMN1 copies on one allele and none on the other allele, the so-called “Silent Carriers” (2+0 genotype). The P460 probemix increases the detection rate of the latter group.

In most populations, approximately 6.3-15.5% of the individuals have two SMN1 copies on a single chromosome 5 strand, of which 0.07-0.19% are a silent carrier. In the African-American population this percentage is even as high as 47.2%, of which 0.41% is a silent carrier (Hendrickson et al 2009). Luo et al. (2014) has reported that a specific SMN1 haplotype block is present in a large percentage of Ashkenazi Jews who carry an SMN1 duplication. This haplotype was also identified on SMN1 duplication alleles in other ethnic groups, but in lower percentages. Detection of the SMN1 polymorphisms g.27134T>G and g.27706-27707delAT can aid in identifying this haplotype and thereby silent carriers.

More information on Spinal Muscular Atrophy is available at http://www.ncbi.nlm.nih.gov/books/NBK1352/.

Regulatory status

SALSA MLPA Probemix P460 SMA (Silent) Carrier is CE-marked under the IVDD for in vitro diagnostic (IVD) use in Europe.

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

SALSA Sample DNA for this product

SALSA Reference Selection & Binning DNA SD084 is an artificial DNA sample with a signal for all probes in the P460 SMA (Silent) Carrier probemix. It has two distinct functions:

  • Assist with peak identification during data analysis. Inclusion of a reaction with SD084 in initial experiments and in experiments following a change in electrophoresis conditions is recommended to aid in the creation of a bin set that links peaks to the probes that produce them.
  • Aid in the selection of suitable reference samples for the P460 SMA (Silent) Carrier probemix. SD084 can be used in initial experiments on DNA samples from healthy individuals from your sample collection with the intention to identify suitable reference samples.

SD084 cannot be used as a reference sample after the initial selection of suitable reference samples from your own sample collection, and cannot be used to quantify the signals of mutation-specific probes.

A vial of SD084 is included with every order of the P460 SMA (Silent) Carrier probemix, but it is possible to order additional vials separately.

For more information, see the product description.

Product documentation

Version A1

Other versions

Contact us for earlier versions.

List prices

Product

Item no.
Description
Technology
Price
P460-025R
SALSA MLPA Probemix P460 SMA (Silent) Carrier – 25 rxn
MLPA
€ 286.00
P460-050R
SALSA MLPA Probemix P460 SMA (Silent) Carrier – 50 rxn
MLPA
€ 560.00
P460-100R
SALSA MLPA Probemix P460 SMA (Silent) 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
SD084
SALSA Reference Selection & Binning DNA SD084 – 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 (A1) version of this product and have been shown to produce useful results.

Coriell Sample ID Copy Number
SMN1 exon 7 SMN1 exon 8 SMN2 exon 7 SMN1 g.27134T>G SMN1 g.27706-27707delAT
NA0023200200
NA0381511100
HG01773114*00
NA1998422111
NA2029433111
HG0288233122
NA1923544033

* 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.

A large set of additional potentially useful positive control samples can be found on the product page of SALSA MLPA Probemix P021 SMA or in Prior et al. (2021).

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P460 SMA (Silent) Carrier

  • Vitello GA et al. (2020). Possible implication of undescribed SMN1-SMN2 genotype in chronic EMG-pattern of SMA with transitory acute denervation. J Musculoskelet Neuronal Interact. 20:610-3.
  • Zhang J et al. (2020). Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in 13,069 Chinese Pregnant Women. J Mol Diagn. 22:817-22.

References

  • Hendrickson BC et al. (2009). Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 46:641-4.
  • 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.
  • Prior TW et al. (2021). Characterization of Reference Materials for Spinal Muscular Atrophy Genetic Testing: A Genetic Testing Reference Materials Coordination Program Collaborative Project. J Mol Diagn. 23:103-10.
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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.