Clinical Characteristics, Genotypes, and Treatment Outcomes in 133 Patients With Spinal Muscular Atrophy: A Retrospective Cohort.

Aim: To characterise spinal muscular atrophy (SMA) phenotypes, genetic profiles, and nusinersen efficacy in China.

Methods: In 133 SMA patients (age 6.38 ± 3.66 years), SMN1 mutations and SMN2 copy numbers were analysed by MLPA and sequencing. Motor function was longitudinally assessed using subtype-specific scales (CHOP-INTEND/HFMSE/RULM/6MWT) at baseline, 6, and 12 months post-nusinersen.

Results: Cohort distribution: type I 31.6% (42/133), II 42.1% (56/133), III 26.3% (35/133). Genetic profiling identified: SMN1 exon7 + 8 deletions (81.2%, 108/133); exon7-only deletions (15.0%, 20/133); and a novel c.884A>T; c.22dup mutation (0.8%). SMN2 copy number inversely correlated with clinical severity (p < 0.001). At 12 months, type I patients showed CHOP-INTEND improvement from 22.0 ± 10.7 to 34.4 ± 14.9 (Δ12.4 ± 8.7; all Δ ≥ 5); type II demonstrated HFMSE Δ3.6 ± 3.4 and RULM Δ3.4 ± 2.1 (1 ambulation milestone); type III exhibited 6MWT gains of 48.8 ± 35.1 m (Δrange 6.0-119.8) with concurrent RULM/HFMSE improvements.

Conclusions: Nusinersen elicited clinically significant motor improvements across SMA subtypes, demonstrating the strongest functional gains in type I (56.4% CHOP-INTEND improvement). We report for the first time a rare case of SMN1 compound heterozygous double-site mutations (c.884A>T; c.22dup).