Brachial amyotrophic diplegia associated with a novel SOD1 mutation (L106P)

Brachial amyotrophic diplegia (BAD) is a subtype of sporadic lower motor neuron disease (LMND) presenting with adult onset, mainly in men, and remaining largely restricted to proximal arm and shoulder girdle muscles without involvement of the lower limbs or appearance of pyramidal signs.1,2 Mutations in the copper/zinc superoxide dismutase (SOD1) gene have been described in familial cases of ALS and occurring in sporadic cases of ALS but not in patients with BAD. We describe a patient with BAD syndrome associated with a novel mutation L106P in SOD1gene. The clinical characteristics of these patients were similar to those reported in other cases of familial ALS with SOD mutations. Of note, the patients with Leu106Val substitution had an earlier age at onset than that observed in our case. L106, an evolutionarily conserved residue among different species, is the major hydrophobic plug for the end of the [beta] barrel, and L106 changes are expected to destabilize the subunit fold. Valine and proline mutants could have a different effect for maintaining the [beta]-barrel fold. Although valine at codon 106 might be expected to alter hydrophobic packing interactions of the side chain into the end of the [beta] barrel, proline at codon 106 might be expected to introduce restriction to the allowed backbone angles along the polypeptide chain turn at one pole of the [beta] barrel and could also affect packing.