Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Lysosomal Storage Diseases
Class Disorders of Carbohydrate Metabolism
Quantity 10 µg
Quantitation Method Please see our FAQ
Cell Type Fibroblast
Transformant Untransformed
Race Caucasian
Family Member 1
Relation to Proband proband
Confirmation Molecular characterization after cell line submission to CCR
ISCN 46,XX[24].arr(1-22,X)x2
Species Homo sapiens
Common Name Human
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).
PDL at Freeze 5.17
Passage Frozen 1
 
L-iduronidase According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.76
 
IDENTIFICATION OF SPECIES OF ORIGIN Species of Origin Confirmed by LINE assay
 
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.
 
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.
Remark 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).
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
 
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
 
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
View pedigree 
Passage Frozen 1
Split Ratio 1:2
Temperature 37 C
Percent CO2 5%
Percent O2 AMBIENT
Medium Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids
Serum 15% fetal bovine serum Not inactivated