Spinal Muscular Atrophy: SMN1 Genotyping

Diagnostic Use

Spinal muscular atrophy (SMA) is characterised by degeneration of lower motor neurons in the spinal cord, causing progressive paralysis of the limbs and trunk, followed by muscle atrophy. SMA is one of the most frequent autosomal recessive diseases, with a carrier frequency of 1 in 50 and is the most common genetic cause of childhood mortality. The phenotype is extremely variable, and patients are classified as SMA type I-III based on age at onset and clinical course. Over 95% of SMA patients display mutations in the survival motor neuron 1 (SMN1) gene on chromosome 5q13, and greater than 96% of these are homozygous for the deletion of exons 7 and 8 of this gene. Genetic analysis for this deletion provides an efficient diagnosis for this disorder.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

SMA gene deletion
SMN1 Deletion Analysis
Spinal Muscular Atrophy Genetic Deletion

Turnaround Time

4 weeks

Test Code

3157

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Pre-testing Requirements

All neonatal referrals <1 month are considered urgent and results will be reported in 5 working days or less.

Please alert the laboratory to any other urgent testing referrals.

Additional Specimen Information

MLPA based assays are sensitive to the buffer used in DNA extraction processes. Due to this, our preference is to recieve whole blood (EDTA) which will then be extracted at Canterbury Health Laboratories. Processing of DNA extracted at other centers may result in a request for a new sample if the analysis is compromised.

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Interpretation

Absence of functional SMN protein results in SMA. Two highly homologous genes, SMN1 and SMN2 encode SMN protein, with SMN1 being the main functional gene. Loss of SMN1 (usually by deletion of exons 7 and 8) is the determining factor in developing SMA. The MLPA assay can distinguish SMN1 from SMN2, overcoming interference which characterised earlier SMA assays. Individuals lacking a functioning copy of SMN1 are always affected, whereas SMA carriers (carrying a single copy of the SMN1 gene) are symptom-free. Establishing the number of SMN2 genes may be of importance in SMA patients – the more SMN2 copies a patient has, the less severe the disease is expected to be. Our SMA assay cannot provide this information.

Reference Intervals

Normal individuals have two copies of the SMN1 gene. SMA carriers usually have one copy. Individuals affected with SMA have no copies of SMN1

Test Method

Patient DNA is analysed for the homozygous deletion of exons 7 and 8 of the SMN1 gene using a multiplex ligatable probe (MLPA) based assay (MRC-Holland P060) followed by detection/quantification on an ABI 3130xl genetic analyser.

Non-Funded Test Cost

$271.81 (Exclusive of GST)

Billing Code

9580

Uncertainty of Measurement:
Caution should be used when interpreting SMA carrier tests. Approximately 4% of normal chromosomes 5 have an SMN1 duplication. This duplication compromises carrier detection since, although two copies of SMN1 are detected, there remains a 50% chance that an allele lacking SMN1 is transmitted to offspring.

Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms / microlitre.
For deletion/duplication analysis of this gene refer to MLPA Testing

Contact Information

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