Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient

Sialidosis is a lysosomal storage disease caused by the deficiency of alpha -N-acetylneuraminidase (NEU1; sialidase), the key enzyme for the intralyso somal catabolism of sialylated glycoconjugates. We have identified a homozy gous transversion in the last intron (IVSE +1 G > C) in neu1 of a sialidosi s patient. Sequencing of the truncated cDNA revealed an alternatively splic ed neu1 transcript which lacks the complete sequence of exon 5. Skipping of exon 5 leads to a frameshift and results in a premature termination codon. This is the first description of an intronic point mutation causing a comp lete deficiency of the lysosomal neuraminidase activity. (C) 2001 Federatio n of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.