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

• Published in: Molecular genetics and metabolism Vol. 93; no. 2; pp. 129 - 133
• Main Authors: Tappino, B., Regis, S., Corsolini, F., Filocamo, M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2008
• Subjects: Alu Elements; Base Sequence; Codon, Nonsense - genetics; DNA Primers - genetics; Exon enhancers; Exon skipping; Exonic Alu insertion; Exons; GlcNAc-1-phosphotransferase; GNPTAB; Heterozygote; Humans; I-cell disease; Infant, Newborn; Male; Microduplication; Molecular Sequence Data; Mucolipidoses - enzymology; Mucolipidoses - genetics; Mucolipidosis type II; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Transferases (Other Substituted Phosphate Groups) - deficiency; Transferases (Other Substituted Phosphate Groups) - genetics; GlcNAc-1-phosphotransferase; GNPTAB; Mucolipidosis type II; I-cell disease; Exon skipping; Exon enhancers; Exonic Alu insertion; Microduplication
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2007.09.010

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.