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 |
3 |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
S685fsX745; MUCOLIPIDOSIS IIIA |
| Identified Mutation |
5-BP DEL, 2215ACTCA |
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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 |
Deficient beta-galactosidase, hexosaminidase, arylsulfatase A, and beta-glucuronidase activity; GlcNAc-Phosphotransferase activity = 2% (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 deletion in exon 13 of the GNPTAB gene [2215_2219delACTCA] resulting in a frameshift and truncation of the protein in the alpha subunit [S685fsX745] 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]. |
| Flint M, Chatterjee P, Lin DL, McMullan LK, Shrivastava-Ranjan P, Bergeron É, Lo MK, Welch SR, Nichol ST, Tai AW, Spiropoulou CF, A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus Nature communications10:285 2018 |
| PubMed ID: 30655525 |
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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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| 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 |
3 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| 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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