NA00798
DNA from Fibroblast
Description:
HURLER SYNDROME
ALPHA-L-IDURONIDASE; IDUA
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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 |
10 µg |
| 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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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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Molecular characterization after cell line submission to CCR
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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 |
5.32 |
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| L-iduronidase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.76 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
IDUA |
| Chromosomal Location |
4p16.3 |
| Allelic Variant 1 |
252800.0001; HURLER SYNDROME |
| Identified Mutation |
TRP402TER; Scott et al. [Genomics 13: 1311 (1992)] found that 31% of MPS I alleles in a study of 64 patients with Hurler syndrome had a trp402-to-ter substitution in the alpha-L-iduronidase protein associated with very severe clinical phenotype in homozygotes. A G-to-A transition at nucleotide 1293 altered the trp-402 codon (TGG) to a stop codon (TAG); translation was terminated approximately two-thirds of the way through the 653-amino acid IDUA protein. Significantly, the index case of Scheie syndrome reported by McKusick et al. [Medicine (Baltimore) 44: 445 (1965)] (M.McC., GM01323), who had been assumed to be a homozygote for a separate allele at the IDUA locus, was found in fact to be a compound heterozygote for the W402X allele. Biochemically, GM01323 fibroblasts had no detectable IDUA protein using 2 different IDUA monoclonal antibodies. They had approximately 0.3% of IDUA activity. This IDUA activity must result from a mild mutation in the other MPS I allele present in the patient. Subsequently, with definition of the mutation in the other allele (see 252800.0004), this proved to be the case. |
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| Gene |
IDUA |
| Chromosomal Location |
4p16.3 |
| Allelic Variant 2 |
252800.0001; HURLER SYNDROME |
| Identified Mutation |
TRP402TER; Scott et al. [Genomics 13: 1311 (1992)] found that 31% of MPS I alleles in a study of 64 patients with Hurler syndrome had a trp402-to-ter substitution in the alpha-L-iduronidase protein associated with very severe clinical phenotype in homozygotes. A G-to-A transition at nucleotide 1293 altered the trp-402 codon (TGG) to a stop codon (TAG); translation was terminated approximately two-thirds of the way through the 653-amino acid IDUA protein. Significantly, the index case of Scheie syndrome reported by McKusick et al. [Medicine (Baltimore) 44: 445 (1965)] (M.McC., GM01323), who had been assumed to be a homozygote for a separate allele at the IDUA locus, was found in fact to be a compound heterozygote for the W402X allele. Biochemically, GM01323 fibroblasts had no detectable IDUA protein using 2 different IDUA monoclonal antibodies. They had approximately 0.3% of IDUA activity. This IDUA activity must result from a mild mutation in the other MPS I allele present in the patient. Subsequently, with definition of the mutation in the other allele (see 252800.0004), this proved to be the case. |
| Remarks |
Clinically affected; deficient alpha-L-iduronidase; Hurler syndrome; homozygous for a TGG>TAG change at nucleotide 1293 in exon 9 of the IDUA gene [Trp402Ter (W402X)]; same subject as GM26656 (stem cell); unaffected mother is GM00799 (fibroblast) and unaffected father is GM00800 (fibroblast).
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| 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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| 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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| Tuyaa-Boustugue P, Jantzen I, Zhang H, Young SP, Broqua P, Tallandier M, Entchev E, Reduction of lysosome abundance and GAG accumulation after odiparcil treatment in MPS I and MPS VI models Molecular genetics and metabolism reports37:101011 2023 |
| PubMed ID: 38053941 |
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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 Pharmaceutics15:101011 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 Genes13:101011 2022 |
| PubMed ID: 35456399 |
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| Baradaran-Heravi A, Balgi AD, Hosseini-Farahabadi S, Choi K, Has C, Roberge M, Effect of small molecule eRF3 degraders on premature termination codon readthrough Nucleic acids research49:3692-3708 2021 |
| PubMed ID: 33764477 |
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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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| Wang J, Zhang Y, Mendonca CA, Yukselen O, Muneeruddin K, Ren L, Liang J, Zhou C, Xie J, Li J, Jiang Z, Kucukural A, Shaffer SA, Gao G, Wang D, AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice Nature604:343-348 2021 |
| PubMed ID: 35322228 |
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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 disease604:343-348 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 sciences22:343-348 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 international22:343-348 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 sciences21:343-348 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 sciences21:343-348 2019 |
| PubMed ID: 32050523 |
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| Makino E, Klodnitsky H, Leonard J, Lillie J, Lund TC, Marshall J, Nietupski J, Orchard PJ, Miller WP, Phaneuf C, Tietz D, Varban ML, Donovan M, Belenki A, Fast, sensitive method for trisaccharide biomarker detection in mucopolysaccharidosis type 1 Scientific reports8:3681 2017 |
| PubMed ID: 29487322 |
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| Xu M, Liu K, Swaroop M, Sun W, Dehdashti SJ, McKew JC, Zheng W, A phenotypic compound screening assay for lysosomal storage diseases Journal of biomolecular screening19:168-75 2013 |
| PubMed ID: 23983233 |
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| Moskowitz SM, Tieu PT, Neufeld EF, Mutation in Scheie syndrome (MPS IS): a G-->A transition creates new splice site in intron 5 of one IDUA allele. Hum Mutat2:141-4 1993 |
| PubMed ID: 8318992 |
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