Novel homozygous ALS2 nonsense mutation (p.Gln715X) in sibs with infantile-onset ascending spastic paralysis: the first cases from northwestern Europe

Abstract

We describe a previously not recognized nonsense mutation in exon 10 of the ALS2 gene in two sibs with infantile-onset ascending spastic paralysis. The mutation predicts chain termination at amino-acid position 715 of the gene product ALSIN (p.Gln715X). The sibs' parents are descendants of a common ancestor who lived in the northern Netherlands during the eighteenth century. This is the first ALS2 mutation detected in northwestern Europeans. The findings emphasize that mutations in ALS2 also need to be considered in patients from northwestern Europe with early-onset spastic paralysis and amyotrophic or primary lateral sclerosis.