A few very rare cases of SMA are accompanied by complex genotypes. In this context, a team of French researchers has identified a novel mutation in a 50 year old patient with type III SMA.
- It took 30 years to solve this complex case.
- The novel mutation corresponded to the insertion of a retrotransposon of type SVA-F (for SINE-VNTR-Alu) and was associated with the classical deletion of the SMN1 gene in the heterozygous state.
- The patient carried only one copy of the paralogous SMN2 gene, in contradiction, only apparently, with his phenotype considered as not very severe.
- Functional studies, including transcriptomic studies, confirmed the pathogenicity of this insertional variant.
Although rare, these complex SMA genotypes are useful to know, not only to refine the diagnosis but also to better understand the pathophysiology of SMA.
