NA02013
DNA from Fibroblast
Description:
MUCOLIPIDOSIS II; ML2; ML II
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 |
| Quantity |
0.050mg |
| Quantitation Method |
Please see our FAQ |
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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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Sample Source
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DNA from Fibroblast
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Race
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White
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Ethnicity
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ARABIAN
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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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| PDL at Freeze |
5.87 |
| Passage Frozen |
14 |
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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 MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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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 |
Y1079fsX1081; MUCOLIPIDOSIS II |
| Identified Mutation |
4-BP DUP, 3395CTAC |
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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 |
Arab; fibroblasts show deficiencies for several lysosomal hydrolases; undetectable level of N-acetylglucosaminylphosphotransferase activity; GlcNAc-Phosphotransferase activity = <0.1% (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 a duplication in exon 16 of the GNPTAB gene [3395_3398dupCTAC] resulting in a frameshift and truncation of the protein in the beta subunit [Y1079fsX1081] 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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| 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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| Kobayashi T, Shinnoh N, Kuroiwa Y, Incorporation and degradation of GM1 ganglioside and asialoGM1 ganglioside in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency. Biochim Biophys Acta875:115-21 1986 |
| PubMed ID: 3079639 |
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| Kobayashi T, Shinnoh N, Goto I, Kuroiwa Y, Hydrolysis of galactosylceramide is catalyzed by two genetically distinct acid beta-galactosidases. J Biol Chem260:14982-7 1985 |
| PubMed ID: 3934152 |
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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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| 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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| Shows TB, Mueller OT, Honey NK, Wright CE, Miller AL, Genetic heterogeneity of I-cell disease is demonstrated by complementation of lysosomal enzyme processing mutants. Am J Med Genet12:343-53 1982 |
| PubMed ID: 6287841 |
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| Butterworth J, Priestman D, Susceptibility to neuraminidase of alpha-L-fucosidase and N-acetyl-beta- D-glucosaminidase of cystic fibrosis, I-cell and neuraminidase- deficient fibroblasts. Clin Chim Acta110:319-26 1981 |
| PubMed ID: 7226536 |
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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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