NA06214
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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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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| PDL at Freeze |
4.87 |
| Passage Frozen |
11 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Chromosome Analysis |
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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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| 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. |
| Cytogenetics |
Chromosome 11: TRANSLOCATION Breakpoint 11q23 t(5;11)11q23 |
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Chromosome 5: TRANSLOCATION Breakpoint 5q22 t(5;11)5q22 |
| Remarks |
Corneal clouding; develop delay; enlarged head; gingival thickening; coarse features; excess MPS in urine; def IDUA & excess MPS in fibro; def corrected to normal level by Hurler factor; 46,XY, t(5;11)pat; Hurler syndrome; homozygous for a TGG>TAG change at nucleotide 1293 in exon 9 of the IDUA gene [Trp402Ter (W402X)] |
| Yi Z, Zhao Y, Yi Z, Zhang Y, Tang G, Zhang X, Tang H, Zhang W, Zhao Y, Xu H, Nie Y, Sun X, Xing L, Dai L, Yuan P, Wei W, Utilizing AAV-mediated LEAPER 20 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice Genome biology24:243 2023 |
| PubMed ID: 37872590 |
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| Qu L, Yi Z, Zhu S, Wang C, Cao Z, Zhou Z, Yuan P, Yu Y, Tian F, Liu Z, Bao Y, Zhao Y, Wei W, Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs Nature biotechnology24:243 2019 |
| PubMed ID: 31308540 |
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| Sarrazin S, Wilson B, Sly WS, Tor Y, Esko JD, Guanidinylated neomycin mediates heparan sulfate-dependent transport of active enzymes to lysosomes Molecular therapy : the journal of the American Society of Gene Therapy18:1268-74 2010 |
| PubMed ID: 20442709 |
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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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