Large-scale population screening for spinal muscular atrophy: clinical implications

Area of Science:

• Genetics
• Population Health
• Neuromuscular Disorders

Background:

• Spinal muscular atrophy (SMA) is a severe genetic disorder.
• Identifying carriers is crucial for genetic counseling and reproductive planning.

Purpose of the Study:

• Determine the carrier frequency of SMN1 deletions in the Israeli population.
• Assess the feasibility and acceptability of population-based SMA screening.

Main Methods:

• Genetic screening of 6394 individuals using multiplex ligation-dependent probe amplification (MLPA).
• MLPA was used to detect SMN1 exon 7 and exon 8 copy number variations.

Main Results:

• A carrier frequency of 1:40 (159 individuals) for SMN1 heterozygous exon 7 deletion was identified.
• Approximately 10.8% of individuals had SMN1 exon 7 in a cis configuration, potentially leading to missed diagnoses.
• Screening acceptance was high (93%) among women undergoing other genetic tests.

Conclusions:

• Current molecular methods may miss up to 5% of SMA carriers due to cis configuration or de novo deletions.
• The estimated carrier detection rate is approximately 90%.
• Population-based SMA screening is deemed feasible and acceptable due to disease severity and carrier frequency.