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

Penzel, Roland; Uhl, Johannes; Kopitz, Jürgen; Beck, Michael; Otto, Herwart F.; Cantz, Michael

doi:10.1016/S0014-5793(01)02645-X

« Previous Next »FEBS Letters
Volume 501, Issue 2 , Pages 135-138, 20 July 2001

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

Edited by Guido Tettamanti

Roland Penzel
- Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
- These authors contributed equally to this work.
- Corresponding author. Fax: (49)-6221-565251
Johannes Uhl
- Department of Pathochemistry and Neurochemistry, University of Heidelberg, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
- These authors contributed equally to this work.
Jürgen Kopitz
- Department of Pathochemistry and Neurochemistry, University of Heidelberg, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
Michael Beck
- Children’s Hospital of the Johannes-Gutenberg University, Langenbeckstrasse 1, D-55131 Mainz, Germany
Herwart F. Otto
- Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
Michael Cantz
- Department of Pathochemistry and Neurochemistry, University of Heidelberg, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany

Received 30 May 2001; received in revised form 21 June 2001; accepted 21 June 2001.

Abstract

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.

Keywords: Lysosomal neuraminidase, Mutation, Donor splice site, Exon skipping, Sialidosis