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 K K-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 s 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. ß

Identification of a CTL4/Neu1 fusion transcript in a sialidosis patient

“…Additionally, no pre‐mRNA and mature mRNA of neu1 were detectable in both patients. The finding of a total lack of neu1 transcripts in our patients is in contrast to the cases so far published [4,6,9,10,12]. It was suggested that a complete absence of lysosomal neuraminidase is lethal during foetal development or at birth [9].…”

“…In view of the fact that even an intronic mutation can cause a complete deficiency of the lysosomal neuraminidase [12], we performed a sequencing‐based screening of genomic DNA from sialidosis patients. In two cases we identified the same 11 kb deletion that encompassed the entire coding region of neu1 .…”

Clinical and Serial MRI Findings of a Sialidosis Type I Patient with a Novel Missense Mutation in the <i>NEU1</i> Gene

“…The age of onset and severity of the clinical manifestations are correlated with NEU1 mutations (10,11) and the level of residual neuraminidase activity (10,12,13), indicating the existence of considerable genotype-phenotype correlation in this disease. To date, more than 40 mutations within the NEU1 gene have been identified in patients with sialidosis type I or type II (2,3,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

A longitudinal study of Taiwanese Sialidosis type 1: an insight into the concept of cherry‐red spot myoclonus syndrome

“…Since then, about 17 genetic confirmed patients from different ethnic groups have been reported with extensive efforts related to the molecular pathology of NEU1 gene without a detailed description of the clinical evaluation. [1,14–21]. Furthermore, comprehensive investigation with multimodality electrophysiological studies and neuroimaging might be currently overlooked.…”