Whole genome sequencing of a brother and sister with an adult-onset form of SMA without mutation in the SMN1 gene revealed a compound heterozygous mutation in the CAPN1 gene. It encodes calpain 1, a ubiquitous calcium-dependent protease.
- The first signs (painless muscle weakness, tendency to fall, cramps in the upper and lower limbs after exercise) appeared around the age of 34, with, however, difficulties in getting up from the ground for the sister since 21.
- Muscle weakness predominated at the roots of the limbs with marked involvement of the quadriceps and triceps.
- CPKs were slightly increased.
- Deltoid muscle biopsy showed chronic neurogenic signs.
- The study of the fibroblasts of the brother and his sister showed:
- a decrease in the level of calpain 1 and its activity;
- a normal level and cellular distribution of the SMN protein.
While we have known since 2016 that mutations in the CAPN1 gene are the cause of a form of spastic and/or ataxic paraplegia (SPG76) beginning in young adulthood, this is the first time that the gene CAPN1 is implicated in a form of SMA.