Description:
MUCOPOLYSACCHARIDOSIS TYPE IVB
GANGLIOSIDOSIS, GENERALIZED GM1, TYPE I
GALACTOSIDASE, BETA-1; GLB1
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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 |
6 |
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| beta-galactosidase |
Giugliani et al (Clin Genet 32:313-325 1987) assayed B-galactosidase activity in this fibroblast culture using 4-methylumbelliferyl B-Dgalactoside and with the alternative artificial substrates: 4MU B-Dfucoside and 4MU A-L-arabinoside. Deficient enzyme activity towards all of these substrates was observed. The respective observed values were 6.4% 2.2% and .7% of normal control activities. Oshima et al (Am J Hum Genet 49:1091-1093 1991) reported that DNA from this Morquio B disease patient had 2 mutations in the B-galactosidase gene: Trp-273>Leu and Trp-509>Cys. EC Number: 3.2.1.23; <6% activity. |
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| beta-galactosidase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.23; 4% activity. |
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| Gene |
GLB1 |
| Chromosomal Location |
3p22.3 |
| Allelic Variant 1 |
611458.0009; MUCOPOLYSACCHARIDOSIS, TYPE IVB |
| Identified Mutation |
TRP273LEU; In 3 affected individuals from 2 unrelated families with Morquio syndrome B (MPS4B; 253010), also known as mucopolysaccharidosis type IVB, Oshima et al. (1991) identified compound heterozygosity for 2 mutations in the GLB1 gene. All patients shared a heterozygous 851-852TG-CT change, resulting in a trp273-to-leu (W273L) substitution, and another pathogenic change (R482H, 611458.0010 and W509C, 611458.0011, respectively). The W273L mutant showed 8% residual enzyme activity, but the other mutations expressed no detectable enzyme activity. |
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| Gene |
GLB1 |
| Chromosomal Location |
3p22.3 |
| Allelic Variant 2 |
611458.0011; MUCOPOLYSACCHARIDOSIS TYPE IVB |
| Identified Mutation |
TRP509CYS; See 611458.0009 and Oshima et al. (1991). The trp509-to-cys (W509C) substitution results from a 1561G-T transversion in the GLB1 gene. The W509C mutant had no residual enzyme activity.
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| Remarks |
Normal N-acetylgalactosamine 6-sulfate sulfatase activity; less than 4% of control B-galactosidase activity using either 4MU-B-gal or GM1 ganglioside; donor subject is a compound heterozygote with two mutations in the GLB1 gene: Trp273Leu (W273L)/Trp509Cys (W509C) |
| Wisniewska K, Gaffke L, Zabinska M, Wegrzyn G, Pierzynowska K, Cellular Organelle-Related Transcriptomic Profile Abnormalities in Neuronopathic Types of Mucopolysaccharidosis: A Comparison with Other Neurodegenerative Diseases Current issues in molecular biology46:2678-2700 2024 |
| PubMed ID: 38534785 |
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| Wisniewska K, Zabinska M, Gaffke L, Szulc A, Walter BM, Wegrzyn G, Pierzynowska K, Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels Frontiers in bioscience (Landmark edition)29:415 2024 |
| PubMed ID: 39735993 |
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| Gaffke L, Pierzynowska K, Cyske Z, Podlacha M, Wegrzyn G, Contribution of vesicle trafficking dysregulation to the pathomechanism of mucopolysaccharidosis Biochemical and biophysical research communications665:107-117 2023 |
| PubMed ID: 37149983 |
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| Zabinska M, Gaffke L, Bielanska P, Podlacha M, Rintz E, Cyske Z, Wegrzyn G, Pierzynowska K, Decreased Levels of Chaperones in Mucopolysaccharidoses and Their Elevation as a Putative Auxiliary Therapeutic Approach Pharmaceutics15:107-117 2023 |
| PubMed ID: 36840025 |
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| Cyske Z, Gaffke L, Pierzynowska K, Wegrzyn G, Complex Changes in the Efficiency of the Expression of Many Genes in Monogenic Diseases, Mucopolysaccharidoses, May Arise from Significant Disturbances in the Levels of Factors Involved in the Gene Expression Regulation Processes Genes13:107-117 2022 |
| PubMed ID: 35456399 |
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| Gaffke L, Szczudlo Z, Podlacha M, Cyske Z, Rintz E, Mantej J, Krzelowska K, Wegrzyn G, Pierzynowska K, Impaired ion homeostasis as a possible associate factor in mucopolysaccharidosis pathogenesis: transcriptomic, cellular and animal studies Metabolic brain disease37:299-310 2021 |
| PubMed ID: 34928474 |
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| Pierzynowska K, Zabinska M, Gaffke L, Cyske Z, Wegrzyn G, Changes in expression of signal transduction-related genes, and formation of aggregates of GPER1 and OXTR receptors in mucopolysaccharidosis cells European journal of cell biology101:151232 2021 |
| PubMed ID: 35537249 |
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| Wisniewska K, Gaffke L, Krzelowska K, Wegrzyn G, Pierzynowska K, Differences in gene expression patterns, revealed by RNA-seq analysis, between various Sanfilippo and Morquio disease subtypes Gene812:146090 2021 |
| PubMed ID: 34896230 |
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| Gaffke L, Pierzynowska K, Krzelowska K, Piotrowska E, Wegrzyn G, Changes in expressions of genes involved in the regulation of cellular processes in mucopolysaccharidoses as assessed by fibroblast culture-based transcriptomic analyses Metabolic brain disease812:146090 2020 |
| PubMed ID: 32886284 |
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| Gaffke L, Pierzynowska K, Rintz E, Cyske Z, Giecewicz I, Wegrzyn G, Gene Expression-Related Changes in Morphologies of Organelles and Cellular Component Organization in Mucopolysaccharidoses International journal of molecular sciences22:146090 2020 |
| PubMed ID: 33803318 |
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| Brokowska J, Pierzynowska K, Gaffke L, Rintz E, Wegrzyn G, Expression of genes involved in apoptosis is dysregulated in mucopolysaccharidoses as revealed by pilot transcriptomic analyses Cell biology international22:146090 2019 |
| PubMed ID: 32125037 |
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| Gaffke L, Pierzynowska K, Podlacha M, Hoinkis D, Rintz E, Brokowska J, Cyske Z, Wegrzyn G, Underestimated Aspect of Mucopolysaccharidosis Pathogenesis: Global Changes in Cellular Processes Revealed by Transcriptomic Studies International journal of molecular sciences21:146090 2019 |
| PubMed ID: 32054071 |
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| Pierzynowska K, Gaffke L, Podlacha M, Wegrzyn G, Genetic Base of Behavioral Disorders in Mucopolysaccharidoses: Transcriptomic Studies International journal of molecular sciences21:146090 2019 |
| PubMed ID: 32050523 |
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| Pshezhetsky AV, Potier M, Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate. J Biol Chem271:28359-65 1996 |
| PubMed ID: 8910459 |
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| Oshima A, Yoshida K, Shimmoto M, Fukuhara Y, Sakuraba H, Suzuki Y, Human beta-galactosidase gene mutations in morquio B disease. Am J Hum Genet49:1091-3 1991 |
| PubMed ID: 1928092 |
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| Giugliani R, Jackson M, Skinner SJ, Vimal CM, Fensom AH, Fahmy N, Sjovall A, Benson PF, Progressive mental regression in siblings with Morquio disease type B (mucopolysaccharidosis IV B). Clin Genet32:313-25 1987 |
| PubMed ID: 3121219 |
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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 |
| Passage Frozen |
6 |
| Split Ratio |
1:5 |
| 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 |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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