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Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient
Author(s) -
Penzel Roland,
Uhl Johannes,
Kopitz Jürgen,
Beck Michael,
Otto Herwart F.,
Cantz Michael
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02645-x
Subject(s) - exon , frameshift mutation , lysosomal storage disease , mutation , microbiology and biotechnology , biology , point mutation , intron , exon skipping , sialidase , neuraminidase , transversion , gene , genetics , enzyme , biochemistry , alternative splicing
Sialidosis is a lysosomal storage disease caused by the deficiency of α‐ 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.