SMN1 mutation spectrum and functional analysis of novel SMN1 variants in a Chinese spinal muscular atrophy cohort.

Spinal muscular atrophy is the most common fatal neurogenetic disorder in infancy and early childhood, caused by insufficient expression of SMN protein due to mutations in the survival motor neuron 1 (SMN1) gene. In this study, we describe the SMN1 mutation spectrum in our SMA cohort and the clinical characteristics of 30 patients with SMN1 compound heterozygous mutations. We find the c.22_23insA hotspot mutation has a founder effect, and identify 6 novel SMN1 variants and verify the pathogenicity of these variants at molecular levels. This study proposes that SMA newborn screening should integrate RT-PCR, MLPA, and long-read sequencing to prevent missed diagnoses of compound heterozygous mutations. Furthermore, in the era of therapeutics, new clinical classification methods based on genetic characteristics are worthy of further exploration.