Molecular characterization of 22 novel UDP-N-acetylglucosamine-1-phosphate transferase α- and β-subunit (GNPTAB) gene mutations causing mucolipidosis types IIα/β and IIIα/β in 46 patients

Barbara Tappino, Nadia A. Chuzhanova, Stefano Regis, Andrea Dardis, Fabio Corsolini, Marina Stroppiano, Emmanuel Tonoli, Tommaso Beccari, Camillo Rosano, Jan Mucha, Mariana Blanco, Marina Szlago, Maja Di Rocco, David N. Cooper, Mirella Filocamo

Research output: Contribution to journalArticlepeer-review

Abstract

Mutational analysis of the GNPTAB gene was performed in 46 apparently unrelated patients with mucolipidosis IIα/β or IIIα/β, characterized by the mistargeting of multiple lysosomal enzymes as a consequence of a UDP-GlcNAc-1-phosphotransferase defect. The GNPTAB mutational spectrum comprised 25 distinct mutant alleles, 22 of which were novel, including 3 nonsense mutations (p.Q314X, p.R375X, p.Q507X), 5 missense mutations (p.I403T, p.C442Y, p.C461G, p.Q926P, p.L1001P), 6 microduplications (c.749dupA, c.857dupA, c.1191-1194dupGCTG, c.1206dupT, c.1331dupG, c.2220-2221dupGA) and 8 microdeletions (c.755-759delCCTCT, c.1399delG, c.1959-1962delTAGT, c.1965delC, c.2550-2554delGAAAA, c.3443-3446delTTTG, c.3487-3490delACAG, c.3523-3529delATGTTCC). All microduplications/ deletions were predicted to result in the premature termination of translation. A novel exonic SNP (c.303G>A; E101E) was identified which is predicted to create an SFRS1 (SF2/ASF) binding site that may be of potential functional/clinical relevance. This study of mutations in the GNPTAB gene, the largest yet reported, extends our knowledge of the mutational heterogeneity evident in MLIIα/β/ MLIIIα/β.

Original languageEnglish
JournalHuman Mutation
Volume30
Issue number11
DOIs
Publication statusPublished - Nov 2009

Keywords

  • GNPTAB
  • Mucolipidosis II
  • Mucolipidosis III
  • Polymorphisms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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