The AmplideX® SMA Plus kit is an in vitro nucleic acid amplification kit for the determination of SMN1 and SMN2 exon 7 copy number. The kit utilises a PCR assay that amplifies distinctive SMN1 and SMN2 gene regions and an endogenous control (EC) gene from purified genomic DNA in a single reaction for up to 94 samples per run. Fluorescently-labelled SMN1- and SMN2-specific amplicons are resolved by capillary electrophoresis (CE) and referenced to co-amplified EC gene products to determine copy numbers. The kit resolves SMN1 and SMN2 exon 7 copy numbers and identifies hybrid peaks associated with chimeric genes resulting from gene conversion. Additionally, the assay determines the status of three important polymorphism variants, including two (c.*3+80T>G and c.*211_*212del) associated with SMN1 gene duplication and one (c.859G>C) associated with reduced disease severity due to improved SMN2 splicing.
Asuragen’s whitepaper ‘Interpreting Variants with the AmplideX® PCR/CE SMN1/2 Plus and SMA Plus Kits’ discusses the latest clinical research on the variants detected by this kit, including how they relate to the underlying genetics and outcomes for spinal muscular atrophy disease prognosis and carrier risk.
Spinal muscular atrophy
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by loss of survival motor neuron 1 (SMN1) gene function and is the primary genetic cause of infant death. SMA is often divided into “types” based on age of onset and maximum motor milestone achievement, with a gradient of phenotypes ranging from never sitting unassisted, with onset prior to six months of age, to adult-onset mild muscular weakness. Most SMA patients are classified into three types in order of decreasing severity: type 1 (~60%), type 2 (~30%), and type 3 (~10%).
How interpreting gene variants improves prognostic predictions for SMA
This whitepaper analyses the latest clinical research on the variants detected by The AmplideX® SMA Plus kit, including how they relate to the underlying genetics and outcomes for spinal muscular atrophy disease prognosis and carrier risk.
Key takeaways from the whitepaper include:
Genetics of SMA carriers
- An increasing body of scientific and clinical evidence suggests that SMN1/2 copy number alone does not provide sufficient information to inform on SMA transmission risk or disease prognosis.
- SMN1 gene duplication variants can help resolve silent SMA carrier status and inform on residual carrier risk in all ethnicities. The paper provides the most comprehensive, up-to-date residual risk estimates available anywhere.
Genetics of SMA prognosis
- A positive SMN2 disease modifier variant status is indicative of improved prognosis in SMA patients and informs likely disease progression. While guidelines emphasise the importance of disease modifiers, this paper describes exactly how to interpret an individuals variant status.
- Whether carrier testing or diagnostic testing, resolving these variants together with SMN1 and SMN2 copy number in a single tube provides more information to the user/patient regardless of testing indications.
Interpreting SMN1 and SMN2 variants
- When the status of variants in SMN1 and SMN2 are relevant and how they can be interpreted based on clinical studies in the available literature.
- Interpretative information provided by SMN1 and SMN2 variants can benefit laboratories and clinicians interested in providing the most accurate, state-of-the-art information for SMA carrier screening and prognostic predictions.