The SMN1 gene deletion test is recommended as the first diagnostic step for a patient suspected to have SMA.
The SMN1 gene deletion test
The deletion status can be tested by using polymerase chain reaction (PCR) to determine if both copies of SMN1 exon 7 are absent, which occurs in 95% of affected individuals. PCR can reliably and accurately measure SMN1 and SMN2 copy numbers over a wide range (i.e. 0–6 copies).1,2
Molecular genetic testing is an important tool in the diagnosis of SMA3,4
Adapted from D’Amico et al.4
Molecular genetic testing using microbead technology has demonstrated:5
High sensitivity (correctly identifying blood samples with SMN1 exon 7 deletions)
High specificity (correctly identifying SMA carriers and unaffected samples as unaffected)
If a patient is found to have a single copy of the SMN1 gene but the clinical presentation is suggestive of SMA, sequencing of the remaining SMN1 gene may identify the mutation and confirm the diagnosis of SMA.
If the individual presenting with symptoms of SMA is shown to have 2 copies of the SMN1 gene, then other motor neuron disorders might be considered in the differential diagnosis.1
Newborn screening
In NSW and the ACT, newborn babies are now screened for SMA, with the condition added to the routine heel prick test.
Although newborn screening is not yet standard practice, time to diagnosis is critical. Based on the natural history of the disease, earlier diagnosis leading to earlier intervention may help improve outcomes for individuals with SMA.6
References
Prior TW. Obstet Gynecol Clin N Am 2010; 37: 23–36.
Butchbach ME. Front Mol Biosci 2016; 3: 7.
Wang CH et al. J Child Neurol 2007; 22: 1027–49.
D’Amico A et al. Orphanet J Rare Dis. 2011; 6: 71.
Pyatt RE et al. Clin Chem 2007; 53: 1879–85.
Rothwell E et al. Am J Med Genet A 2013; 161A: 679–86.
