An Alu insertion in compound heterozygosity with a microduplication in GNPTAB gene underlies Mucolipidosis II

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Abstract

Mucolipidosis type II (ML II) is a fatal, autosomal recessive, lysosomal storage disorder characterized by severe clinical and radiologic features. ML II results from mutations in alpha and beta subunits, encoded by the GlcNAc-1-phosphotransferase gene (GNPTAB). Most of the 40 different GNPTAB mutations reported so far are insertions and deletions predicting diverse types of aberrant proteins. Alu mobile elements have however never been involved in these events up to now. The Italian ML II patient of our study showed an Alu retrotrasposition in GNPTAB exon 5. The Alu insertion mutation (NM_024312.3:c.555_556insHSU14569) generated a transcript with a skipping of the target exon 5 and a frameshift p.S122fs, causing a premature translation termination codon at position 123. This insertion mutation was found in compound heterozygosity with the frameshift p.S887KfsX33, resulting from a new mono-nucleotide duplication (c.2659dupA) that occurred in GNPTAB exon 13. A possible involvement of cis-splicing elements having an exonic location, such as exon enhancers (ESEs), is discussed as mechanism that led to the production of the aberrant mRNA splicing.

Original languageEnglish
Pages (from-to)129-133
Number of pages5
JournalMolecular Genetics and Metabolism
Volume93
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Exon enhancers
  • Exon skipping
  • Exonic Alu insertion
  • GlcNAc-1-phosphotransferase
  • GNPTAB
  • I-cell disease
  • Microduplication
  • Mucolipidosis type II

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

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