TY - JOUR
T1 - 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
AU - Tappino, Barbara
AU - Chuzhanova, Nadia A.
AU - Regis, Stefano
AU - Dardis, Andrea
AU - Corsolini, Fabio
AU - Stroppiano, Marina
AU - Tonoli, Emmanuel
AU - Beccari, Tommaso
AU - Rosano, Camillo
AU - Mucha, Jan
AU - Blanco, Mariana
AU - Szlago, Marina
AU - Di Rocco, Maja
AU - Cooper, David N.
AU - Filocamo, Mirella
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - GNPTAB
KW - Mucolipidosis II
KW - Mucolipidosis III
KW - Polymorphisms
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U2 - 10.1002/humu.21099
DO - 10.1002/humu.21099
M3 - Article
C2 - 19634183
AN - SCOPUS:70350705967
VL - 30
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 11
ER -