Description:
MUCOLIPIDOSIS II; ML2; ML II
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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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Family Member
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1
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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 |
15 |
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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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| UDP-N-acetylglucosamine--lysosomal-enzyme N-acetylglucosaminephosphotransferase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.7.8.17; 0% activity. |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
R46X; MUCOLIPIDOSIS II |
| Identified Mutation |
ARG46TER |
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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 |
Low levels of activity for several lysosomal enzymes; same patient as GM01423; undetectable level of N-acetylglucosaminylphosphotransferase activity; donor subject is a compound heterozygote: one allele has a C>T transition at nucleotide 136 of the GNPTAB gene [136C>T] resulting in a substitution of a termination codon for arginine at codon 46 [Arg46Ter (R46X)] and a second allele has a two basepair deletion at nucleotide 3503 [3503 delTC] of the GNPTAB gene
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| 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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| Valenzano KJ, Kallay LM, Lobel P, An assay to detect glycoproteins that contain mannose 6-phosphate. Anal Biochem209:156-62 1993 |
| PubMed ID: 8465950 |
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| Brauker JH, Wang JL, Nonlysosomal processing of cell-surface heparan sulfate proteoglycans. Studies of I-cells and NH4Cl-treated normal cells. J Biol Chem262:13093-101 1987 |
| PubMed ID: 2958450 |
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| Brown WJ, Farquhar MG, Accumulation of coated vesicles bearing mannose 6-phosphate receptors for lysosomal enzymes in the Golgi region of I-cell fibroblasts. Proc Natl Acad Sci U S A81:5135-9 1984 |
| PubMed ID: 6147848 |
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| Honey NK, Miller AL, Shows TB, The mucolipidoses: identification by abnormal electrophoretic patterns of lysosomal hydrolases. Am J Med Genet9:239-53 1981 |
| PubMed ID: 7282783 |
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| Koch G, Lalley PA, McAvoy M, Shows TB, Assignment of LIPA, associated with human acid lipase deficiency, to human chromosome 10 and comparative assignment to mouse chromosome 19. Somatic Cell Genet7:345-58 1981 |
| PubMed ID: 7292252 |
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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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| Varki A, Kornfeld S, Identification of a rat liver alpha-N-acetylglucosaminyl phosphodiesterase capable of removing "blocking" alpha-N- acetylglucosamine residues from phosphorylated high mannose oligosaccharides of lysosomal enzymes. J Biol Chem255:8398-401 1980 |
| PubMed ID: 6251056 |
| Passage Frozen |
15 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| 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 |
| Supplement |
- |
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