NA01256
DNA from Fibroblast
Description:
SCHEIE 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 |
| 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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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 |
6.55 |
| Passage Frozen |
13 |
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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 |
252800.0004; SCHEIE SYNDROME |
| Identified Mutation |
IVS5AS, G>A, -7; In the fibroblast strain GM01323 derived from the index case of the Scheie syndrome reported by McKusick et al. [Medicine (Baltimore) 44: 445 (1965)] and in a second cell line, GM01256, Moskowitz et al. [Hum Mutat 2: 71 (1993)] found compound heterozygosity for the same 2 mutations: a G-to-A transition in intron 5, in position -7 from exon 6, and a W402X change (TGG to TAG) in exon 9. The latter mutation, trp402-to-ter (252800.0001), had previously been identified as a common MPS I mutation in the Caucasian population, present in homozygosity in some Hurler patients and in compound heterozygosity in patients with any form of MPS I, including the Scheie patient GM01323 [Scott et al., Genomics 13: 1311 (1992)]. |
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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 |
Deficient Alpha-L-Iduronidase; Scheie syndrome; compound heterozygote: a G>A transition in intron 5, in position -7 from exon 6 (IVS5AS-7G>A) and TGG>TAG at nucleotide 1293 in exon 9 of the IDUA gene [Trp402Ter (W402X)] |
| Swaroop M1, Brooks MJ2, Gieser L2, Swaroop A2, Zheng W1., Patient iPSC-derived neural stem cells exhibit phenotypes in concordance with the clinical severity of Mucopolysaccharidosis I Human Molecular Genetics: 2018 |
| PubMed ID: 30052969 |
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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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| 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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