title: Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient.
abstract: Sialidosis is a lysosomal storage disease caused by the deficiency of alpha-N-acetylneuraminidase (NEU1; sialidase), the key enzyme for the intralysosomal catabolism of sialylated glycoconjugates. We have identified a homozygous transversion in the last intron (IVSE +1 G>C) in neu1 of a sialidosis patient. Sequencing of the truncated cDNA revealed an alternatively spliced 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 complete deficiency of the lysosomal neuraminidase activity.
authors.affiliation: Institute of Pathology, University of Heidelberg, Germany. roland_penzel@med.uni-heidelberg.de
authors.forename: R
authors.initials: R
authors.lastname: Penzel
authors.forename: J
authors.initials: J
authors.lastname: Uhl
authors.forename: J
authors.initials: J
authors.lastname: Kopitz
authors.forename: M
authors.initials: M
authors.lastname: Beck
authors.forename: H F
authors.initials: HF
authors.lastname: Otto
authors.forename: M
authors.initials: M
authors.lastname: Cantz
mesh_terms: D000595:Amino Acid Sequence; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D022821:RNA Splice Sites; C486385:NEU1 protein, human; D009439:Neuraminidase