Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA). A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c.859G>C variant in SMN2 has been recently reported as a positive disease modifier. We identified the variant in 10 unrelated chronic SMA patients with a wide spectrum of phenotypes ranging from type II patients who can only sit to adult walkers. Haplotype analysis strongly suggests that the variant originated from a common ancestor. Our results confirm that the c.859G>C variant is a milder SMN2 allele and predict a direct correlation between SMN activity and phenotypic severity.
- Clinical genetics
- molecular genetics
- motor neurone disease
- neuromuscular disease
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Funding Other funders: GENAME Project, CIBERER Intramural U-705 and FIS08-0729.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Hospital Santa Creu i Sant Pau, Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.