Novel point mutations in survival motor neuron 1 gene expand the spectrum of phenotypes observed in spinal muscular atrophy patients

The aim of our study was to identify point mutations in a group of 606 patients diagnosed for spinal muscular atrophy with excluded biallelic loss of the SMN1 gene. Point missense mutations or small deletions in the SMN1 gene were ultimately identified in 18 patients. Six patients were found to have small deletions, the c.429_435del mutation in 3 cases, the c.431delC mutation in 2 and c.722delC in one. Those mutations, not described previously, were characteristic of patients presenting a severe phenotype. The most frequent missense mutation – p.Thr274Ile, was identified in 9 patients presenting a rather mild phenotype. Three other missense mutations, i.e. p.Ser230Leu, p.Ala111Gly and p.Pro244Leu, were identified in a further 3 SMA3 patients. Mutation p.Pro244Leu, not described so far, was identified in a patient with a mild form of SMA and more distal distribution of muscle weakness. Our results suggest a specific point mutation spectrum in the Polish population. The existence of small deletions not identified thus far could suggest a possible founder effect. In patients with preserved one SMN1 allele without common exon 7 deletion, presenting a mild form of SMA, a special consideration should be given to the p.Thr274Ile mutation.