Description:
MUCOLIPIDOSIS IIIA
N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
6 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
D190fsX211; MUCOLIPIDOSIS IIIA |
| Identified Mutation |
733A>T |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 2 |
607840.0011; MUCOLIPIDOSIS II |
| Identified Mutation |
2-BP DEL, 3665TC; In 8 of 9 pedigrees with ML II (252500) and 5 of 7 with ML IIIA (252600), Kudo et al. (Am J Hum Genet 78:451-463, 2006) identified a frameshift mutation in the GNPTAB gene consisting of deletion of 2 nucleotides (3665_3666delTC) beginning at leu1168 and leading to premature termination at amino acid 1172 (L1168fsX1172). This mutation was the most frequent in their study and was found in both the homozygous and compound heterozygous state, in combination with severe mutations (i.e., mutations preventing the generation of active enzyme) in ML II and with mild mutations (i.e., mutations allowing the generation of active enzyme) in ML IIIA. |
| Remarks |
Similarly affected sister; deficient fibroblast B-hexosaminidase, B-galactosidase, B-glucuronidase, A-fucosidase, A-galactosidase, A-mannosidase, and GLcNAc phosphotransferase activity; complementation group A; GlcNAc-Phosphotransferase activity = 0.8% (measured as specific activity in cell lysate and reported as percentage of activity in normal fibroblasts); donor subject is a compound heterozygote: one allele has an A>T transversion in exon 5 of the GNPTAB gene [733A>T] resulting in mRNA with a 4-bp deletion causing a frameshift at the 3'-end of the exon 5 sequence [D190fsX211] and a second allele has a 2-bp deletion in exon 19 of the GNPTAB gene [3665_3666delTC] resulting in a frameshift and truncation of the protein in the beta subunit [L1168fsX1172]. |
| Kudo M, Brem MS, Canfield WM, Mucolipidosis II (I-Cell Disease) and Mucolipidosis IIIA (Classical Pseudo-Hurler Polydystrophy) Are Caused by Mutations in the GlcNAc-Phosphotransferase alpha / beta -Subunits Precursor Gene. Am J Hum Genet78(3):451-63 2006 |
| PubMed ID: 16465621 |
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| Little LE, Mueller OT, Honey NK, Shows TB, Miller AL, Heterogeneity of N-acetylglucosamine 1-phosphotransferase within mucolipidosis III. J Biol Chem261:733-8 1986 |
| PubMed ID: 3001079 |
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| Honey NK, Mueller OT, Little LE, Miller AL, Shows TB, Mucolipidosis III is genetically heterogeneous. Proc Natl Acad Sci U S A79:7420-4 1982 |
| PubMed ID: 6961420 |
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| Robey PG, Neufeld EF, Defective phosphorylation and processing of beta-hexosaminidase by intact cultured fibroblasts from patients with mucolipidosis III. Arch Biochem Biophys213:251-7 1982 |
| PubMed ID: 6460470 |
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| Reitman ML, Varki A, Kornfeld S, Fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5'-diphosphate-N- acetylglucosamine: glycoprotein N-acetylglucosaminylphosphotransferase activity. J Clin Invest67:1574-9 1981 |
| PubMed ID: 6262380 |
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| Varki AP, Reitman ML, Kornfeld S, Identification of a variant of mucolipidosis III (pseudo-Hurler polydystrophy): a catalytically active N- acetylglucosaminylphosphotransferase that fails to phosphorylate lysosomal enzymes. Proc Natl Acad Sci U S A78:7773-7 1981 |
| PubMed ID: 6461005 |
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| Potier M, Mameli L, Belisle M, Dallaire L, Melancon SB, Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferyl- alpha-D-N-acetylneuraminate) substrate. Anal Biochem94:287-96 1979 |
| PubMed ID: 464297 |
| Passage Frozen |
6 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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