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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Black/African American
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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 |
2 |
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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 |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
Q278X; MUCOLIPIDOSIS IIIA |
| Identified Mutation |
GLN278TER |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 2 |
607840.0013; MUCOLIPIDOSIS IIIA |
| Identified Mutation |
IVS17DS,T>G,+6; In a family with 2 affected sibs and in 2 patients with mucolipidosis IIIA (252900), Kudo et al. (Am J Hum Genet 78:451-463, 2006) described a donor splice site mutation in intron 17 of the GNPTAB gene, IVS17+6T-G, that results in skipping of exon 17 and frameshift with a premature termination at residue 1085 (P1084fsX1172). This same result was observed in another intron 17 splice site mutation in a patient with ML II (607840.0012). The former intron 17 splice site mutation was designated type I and the latter type II. Although the mRNA sequences derived from these 2 mutations are the same, the GlcNAc-phosphotransferase activities and clinical outcomes are different; fibroblasts with the type I mutation exhibited less than 0.1% activity, whereas those carrying the type II mutation exhibited 1 to 3% GlcNAc-phosphotransferase activity. That the type II mutation was located outside the invariant splice site was suggested as a possible cause of the greater activity. |
| Remarks |
Similarly affected sib; deficient fibroblast B-hexosaminidase, B-galactosidase, A-fucosidase, A-galactosidase, A-mannosidase, and N-acetylglucosaminylphosphotransferase activity; complementation group A; GlcNAc-Phosphotransferase activity = 3% (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 C>T transition at nucleotide 996 in exon 8 of the GNPTAB gene [996C>T] resulting in a substitution of a stop codon for glutamine at codon 278 [Gln278Ter (Q278X)] and a second allele has a donor splice site mutation in intron 17 of the GNPTAB gene [IVS17+6T>G] resulting in the skipping of exon 17 and a frameshift with a premature termination at residue 1085 [P1084fsX1085]. |
| 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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| Varki A, Reitman ML, Vannier A, Kornfeld S, Grubb JH, Sly WS, Demonstration of the heterozygous state for I-cell disease and pseudo- Hurler polydystrophy by assay of N-acetylglucosaminylphosphotransferase in white blood cells and fibroblasts. Am J Hum Genet34:717-29 1982 |
| PubMed ID: 6289658 |
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| Andria G, Sly WS, Intermediate golgi alpha-D-mannosidosis and mucolipidosis II and III. Pediatr Res15:70-3 1981 |
| PubMed ID: 7208171 |
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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 |
| Passage Frozen |
2 |
| Split Ratio |
1:5 |
| 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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