The first nonsense mutation in alsin results in a homogeneous phenotype of infantile‐onset ascending spastic paralysis with bulbar involvement in two siblings

Eight mutations in the ALS2 gene have been described as causing autosomal‐recessive juvenile‐onset forms of the motor neuron diseases amyotrophic lateral sclerosis, primary lateral sclerosis and hereditary spastic paraplegia. All mutations are small deletions that are predicted to result in a frameshift and premature truncation of the alsin protein. Here we describe a ninth ALS2 mutation, in two siblings affected by infantile‐onset ascending spastic paraplegia with bulbar involvement. This mutation is predicted to result in the substitution of an amino acid by a stop codon, and thus is the first nonsense mutation detected in this gene. It is probable that full‐length alsin is required for the proper development and/or functioning of upper motor neurons.