Application of whole genome sequencing for carrier and diagnostic assessment of spinal muscular atrophy in Taiwan.

This study aimed to evaluate the feasibility of whole-genome sequencing (WGS) combined with computational tools for spinal muscular atrophy (SMA) carrier screening and disease diagnosis in Taiwan. WGS data from 1492 Taiwan Biobank participants and two patients with SMA were analysed to determine the SMN1 and SMN2 copy numbers using Illumina DRAGEN SMN Caller and validated by multiplex ligation-dependent probe amplification (MLPA). Among 1480 samples analysed, 23 SMA carriers were identified, yielding a carrier frequency of 1.55%. MLPA confirmed the accuracy of SMN1 and SMN2 copy number results detected using WGS. Both patients with SMA presented compound heterozygous variants with one SMN1 copy loss and the other SMN1 variant, specifically SMN1,c.815A>G, and SMN1,c.81+2_81+3delTG, respectively. Taken together, combining WGS with advanced bioinformatics tools is a feasible and promising approach for SMA carrier screening and disease diagnosis.