A novel HEXB mutation and its structural effects in juvenile Sandhoff disease

Mutations in HEXB, encoding the p-subunit common to hexosaminidases A and B, cause the neurodegenerative condition, Sandhoff disease. A homozygous missense HEXB Mutation (p. D459A) was discovered in six patients with a rare juvenile variant: we show that this disrupts a salt bridge between aspartate D459 and arginine 505 at the subunit interface; R505 mutations are reported in late-onset Sandhoff disease. Identification of D459A contributes to diagnosis and molecular understanding of attenuated Sandhoff disease variants. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.