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 Neil ORCID: https://orcid.org/0000-0002-8943-8484 and Filocamo, Mirella 2009. 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. Human Mutation 30 (11) , E956-E973. 10.1002/humu.21099 |
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 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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | Q Science > QH Natural history > QH426 Genetics |
Uncontrolled Keywords: | Mucolipidosis II; Mucolipidosis III; GNPTAB; polymorphisms |
Publisher: | Wiley-Blackwell |
ISSN: | 1059-7794 |
Last Modified: | 19 Oct 2022 09:56 |
URI: | https://orca.cardiff.ac.uk/id/eprint/22728 |
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