The clinical utility of a risk-modifying SNP to detect carriers for spinal muscular atrophy with increased...

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease caused by biallelic inactivation of the survival motor neuron 1 (SMN1) gene. With a prevalence of ~1 in 11,000 live births (carrier frequency of ~1:50), SMA is one of the most common severe childhood-onset diseases; therefore, current guidelines recommend pan-ethnic carrier screening for SMA before or during pregnancy. Routine SMN1 copy number assessment detects ~96% of all SMA carriers, but not the remaining 4% who harbor two copies of SMN1 arrayed in -cis [2 + 0]. The c.*3+80T>G risk-modifying SNP positively correlates with this chromosomal configuration and may be used to modify the residual risk of being a carrier for SMA.

One year after incorporating the detection of the c.*3+80>G risk-modifying SNP into our routine SMA carrier screen, we perform a retrospective chart review to evaluate its frequency and utilization in the prenatal clinic.

In comparison with classic carriers for SMA, study data show that individuals with two copies of SMN1 and the risk modifier were counseled less frequently about their increased risk of being a carrier for SMA.

Incorporating the c.*3+80T>G risk-modifying SNP is important for detecting carriers for SMA with a higher clinical sensitivity.