Description:
MUCOLIPIDOSIS II; ML2; ML II
N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
|
Cell Type
|
Fibroblast
|
|
Transformant
|
Untransformed
|
|
Race
|
White
|
|
Family Member
|
1
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| PDL at Freeze |
5.77 |
| Passage Frozen |
11 |
| |
| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
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. |
| |
| 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 |
Reduced B-galactosidase activity in skin fibroblasts; serum studies compatible with diagnosis; culture grows poorly; GlcNAc-Phosphotransferase activity = <0.1% (measured as specific activity in cell lysate and reported as percentage of activity in normal fibroblasts); donor subject is homozygous for 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]. |
| 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 |
| |
| Leroy JG, Sillence D, Wood T, Barnes J, Lebel RR, Friez MJ, Stevenson RE, Steet R, Cathey SS, A novel intermediate mucolipidosis II/IIIaß caused by GNPTAB mutation in the cytosolic N-terminal domain European journal of human genetics : EJHG22:594-601 2013 |
| PubMed ID: 24045841 |
| |
| 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 |
| |
| Quinn CM, Kågedal K, Terman A, Stroikin U, Brunk UT, Jessup W, Garner B, Induction of fibroblast apolipoprotein E expression during apoptosis, starvation-induced growth arrest and mitosis The Biochemical journal378:753-61 2003 |
| PubMed ID: 14656220 |
| |
| 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 |
| |
| Sando GN, Henke VL, Recognition and receptor-mediated endocytosis of the lysosomal acid lipase secreted by cultured human fibroblasts. J Lipid Res23:114-23 1982 |
| PubMed ID: 7057100 |
| |
| 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 |
| |
| Tietze F, Butler JD, Elevated cystine levels in cultured skin fibroblasts from patients with I-cell disease. Pediatr Res13:1350-5 1979 |
| PubMed ID: 523195 |
| |
| Ben-Yoseph Y, Burton BK, Nadler HL, Quantitation of the enzymically deficient cross reacting material in GM1 gangliosidoses. Am J Hum Genet29:575-80 1977 |
| PubMed ID: 412418 |
| Passage Frozen |
11 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
|
|