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Molecular characterization of 22 novel UDP-N-acetylglucosamine-1-phosphate transferase alpha- and beta-subunit (GNPTAB) gene mutations causing mucolipidosis types IIalpha/beta and IIIalpha/beta in 46 patients.

Abstract
Mutational analysis of the GNPTAB gene was performed in 46 apparently unrelated patients with mucolipidosis IIalpha/beta or IIIalpha/beta, 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 micro-duplications/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 MLIIalpha/beta/MLIIIalpha/beta.
AuthorsBarbara 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
JournalHuman mutation (Hum Mutat) Vol. 30 Issue 11 Pg. E956-73 (Nov 2009) ISSN: 1098-1004 [Electronic] United States
PMID19634183 (Publication Type: Journal Article)
Chemical References
  • Codon, Nonsense
  • Transferases (Other Substituted Phosphate Groups)
  • GNPTAB protein, human
Topics
  • Adolescent
  • Adult
  • Animals
  • COS Cells
  • Child
  • Child, Preschool
  • Chlorocebus aethiops
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Genetic Association Studies
  • Genotype
  • Humans
  • Infant
  • Mucolipidoses (genetics)
  • Mutation
  • Mutation, Missense
  • Sequence Deletion
  • Transferases (Other Substituted Phosphate Groups) (genetics)

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