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

作者：Tappino B; Regis S; Corsolini F; Filocamo M^*

来源：Molecular Genetics and Metabolism, 2008, 93(2): 129-133.

DOI：10.1016/j.ymgme.2007.09.010

• mucolipidosis type 11
• I-cell disease
• GlcNAe-l-phosphotransferase
• GNPTAB
• exon skipping
• exonic alu insertion
• microduplication
• exon
• enhancers

Mucolipidosis type II (ML II) is a fatal, autosomal recessive, lysosomal storage disorder characterized by severe clinical and radiologic features. ML 11 results from mutations in alpha and beta subunits, encoded by the GleNAc-l-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 11 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.

• 出版日期2008-2