Premium
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
Author(s) -
Tappino Barbara,
Chuzhanova Nadia A.,
Regis Stefano,
Dardis Andrea,
Corsolini Fabio,
Stroppiano Marina,
Tonoli Emmanuel,
Beccari Tommaso,
Rosano Camillo,
Mucha Jan,
Blanco Mariana,
Szlago Marina,
Di Rocco Maja,
Cooper David N.,
Filocamo Mirella
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21099
Subject(s) - mucolipidosis , biology , genetics , nonsense mutation , missense mutation , gene , microbiology and biotechnology , exon , mutation , mutant , progressive myoclonus epilepsy , point mutation , stop codon , enzyme , biochemistry
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 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 MLIIα/β/MLIIIα/β. © 2009 Wiley‐Liss, Inc.