The results support efforts to achieve drug-induced mutation suppression of stop codons. The immunogenic epitope resulting from readthrough emphasizes the importance of monitoring T-cell immunity during clinical studies that suppress stop codons. Similar principles apply to other molecular strategies, including exon skipping and gene therapy.

Hereditary spastic paraplegia is a heterogeneous group of inherited neurodegenerative disorders in which the predominant clinical feature is gait disturbance owing to spasticity and weakness of the lower limbs. Autosomal dominant hereditary spastic paraplegia is the predominant form of the disorder. To date, 10 autosomal dominant hereditary spastic paraplegia gene loci and genes for 6 of them have been identified. Spastic paraplegia 6, with a typical teenage onset and considered to be one of the more severe forms of the disease, is due to mutations in the gene NIPA1. We report a childhood-onset, aggressive, spastic paraparesis in a North American family with a c.316G>A mutation of the NIPA1 gene, confirming c.316 as a mutational hot spot.

Hereditary neuralgic amyotrophy (HNA), an autosomal dominant disorder associated with SEPT9 mutation located on chromosome 17q25, causes recurrent painful weakness with sensory disturbances in a brachial distribution. We present electrophysiological, clinical phenotype, and molecular genetic data of three members from a family with HNA with the C262T SEPT9 mutation. The degree of motor weakness and recovery is variable within this family. Severity and recovery from motor deficits may have been a function of comorbid medical conditions. To our knowledge, this is the first report to confirm SEPT9 mutation in a family with suspected HNA.