Description:
HURLER-SCHEIE SYNDROME
CYTOCHROME P450, SUBFAMILY IID, POLYPEPTIDE 6; CYP2D6
CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 19; CYP2C19
CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9
VITAMIN K EPOXIDE REDUCTASE COMPLEX, SUBUNIT 1; VKORC1
UDP-GLYCOSYLTRANSFERASE 1 FAMILY, POLYPEPTIDE A1; UGT1A1
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
Pharmacogenetics
GeT-RM Samples |
| Class |
Disorders of Carbohydrate Metabolism |
| Alternate IDs |
GM17042 [HURLER-SCHEIE SYNDROME] |
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GM17332 [HURLER-SCHEIE SYNDROME] |
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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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Ethnicity
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MIDDLE EASTERN; ARAB;
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Family Member
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2
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Relation to Proband
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mother
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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 |
5.22 |
| Passage Frozen |
9 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| Pharmacogenomics Panel |
For pharmacogenetic variants please click here: GeT-RM PGx Search |
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| HLA TYPING |
For HLA variants please click here: HLA Panel |
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| Gene |
CYP2D6 |
| Chromosomal Location |
22q13.1 |
| Allelic Variant 1 |
T107I; R296C; S486T; DEBRISOQUINE, POOR METABOLISM OF |
| Identified Mutation |
THR107ILE, ARG296CYS, AND SER486THR; This allelic variant is also known as CYP2D6*17 or CYP2D6(Z). Oscarson et al (Mol Pharmacol 52(6):1034-40, 1997) found that in many black African populations, the capacity for CYP2D6-dependent drug metabolism is generally reduced. A specific variant of the CYP2D6 gene (CYP2D6*17) that carries three functional mutations (T107I, R296C, and S486T) has been found to be present in Zimbabwean subjects with impaired CYP2D6-dependent hydroxylase activity. |
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| Gene |
IDUA |
| Chromosomal Location |
4p16.3 |
| Allelic Variant 1 |
252800.0005; HURLER SYNDROME |
| Identified Mutation |
GLY409ARG AND TER654CYS; In a patient with Hurler syndrome in a consanguineous Muslim Arab family in Gaza, Bach et al. (1993) observed homozygosity for an IDUA allele containing 2 amino acid substitutions: a G-to-C transversion in exon 9 converting codon 409 from GGG (gly) to CGG (arg), and an A-to-T transversion in the termination codon 654 (TGA), converting it to a cys (TGT) residue. The cDNA sequence predicted an extension of 38 amino acids before the next termination codon was reached. Both mutations were found in heterozygous form in the DNA of each parent. Expression of cDNA mutagenized at one or both positions showed that gly409-to-arg caused a reduction of less than half the alpha-L-iduronidase activity, whereas the ter-to-cys mutation reduced activity by 98% compared with expression of normal cDNA.
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| Gene |
CYP2D6 |
| Chromosomal Location |
22q13.1 |
| Allelic Variant 2 |
124030.0008; CODEINE, ULTRARAPID METABOLISM OF |
| Identified Mutation |
DUP; Gasche et al (New Eng J Med 351:2827-2831, 2004) described a patient who had developed life-threatening opioid intoxication after he was given small doses of codeine for the treatment of cough associated with bilateral pneumonia. CYP2D6 genotyping showed 3 or more functioning alleles, as a result of gene duplication, resulting in high levels of morphine and morphine-6 glucuronide. |
| Remarks |
Clinically unaffected mother of affected child (GM01898); The following datasets were obtained and reported by the GeT-RM program: HLA variants (HLA-A*02:01/*30:02, HLA-B*53:01/*58:01, HLA-C*04:01/*07:01, HLA-DRB1*08:04/*14:01, HLA-DQB1*04:02/*05:01); pharmacogenomic variants ( CYP2D6*2XN/*17, CYP2C19*1/*2, CYP2C9*1/*1, VKORC1*WT/-1639G>A, UGT1A1*1/*1).
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| Pratt VM, Turner A, Broeckel U, Dawson DB, Gaedigk A, Lynnes TC, Medeiros EB, Moyer AM, Requesens D, Ventrini F, Kalman LV, Characterization of Reference Materials for CYP2C9, CYP2C19, VKORC1, CYP2C Cluster Variant, GGCX, and Other Pharmacogenetic Alleles with an Association for Molecular Pathology (AMP) Pharmacogenetics Working Group Tier 2 Status - A GeT-RM Collaborative Project The Journal of molecular diagnostics : JMD: 2021 |
| PubMed ID: 34020041 |
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| Scott SA, Scott ER, Seki Y, Chen AJ, Wallsten R, Owusu Obeng A, Botton MR, Cody N, Shi H, Zhao G, Brake P, Nicoletti P, Yang Y, Delio M, Shi L, Kornreich R, Schadt EE, Edelmann L, Development and Analytical Validation of a 29 Gene Clinical Pharmacogenetic Genotyping Panel: Multi-Ethnic Allele and Copy Number Variant Detection Clinical and translational science14:204-213 2021 |
| PubMed ID: 32931151 |
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| Ramudo-Cela L, López-Martí JM, Colmeiro-Echeberría D, De-Uña-Iglesias D, Santomé-Collazo JL, Monserrat-Iglesias L, Development and validation of a next-generation sequencing panel for clinical pharmacogenetics Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria44:243-253 2020 |
| PubMed ID: 33156743 |
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| Bettinotti MP1, Ferriola D2, Duke JL2, Mosbruger TL2, Tairis N2, Jennings L3, Kalman LV4, Monos D5., Characterization of 108 Genomic DNA Reference Materials for 11 Human Leukocyte Antigen Loci: A GeT-RM Collaborative Project. Journal of Molecular Diagnostics18:30111-30119 2018 |
| PubMed ID: 29959025 |
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| Swart M, Stansberry WM, Pratt VM, Medeiros EB, Kiel PJ, Shen F, Schneider BP, Skaar TC, Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology The Journal of molecular diagnostics : JMD21:491-502 2018 |
| PubMed ID: 30794985 |
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| Langaee T, Hamadeh I, Chapman AB, Gums JG, Johnson JA, A novel simple method for determining CYP2D6 gene copy number and identifying allele(s) with duplication/multiplication PloS one10:e0113808 2014 |
| PubMed ID: 25625348 |
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| Lee CC, McMillin GA, Babic N, Melis R, Yeo KT, Evaluation of a CYP2C19 genotype panel on the GenMark eSensor® platform and the comparison to the Autogenomics Infiniti™ and Luminex CYP2C19 panels Clinica chimica acta; international journal of clinical chemistry412(11-12):133-7 2010 |
| PubMed ID: 21385571 |
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| Pratt VM, Zehnbauer B, Wilson JA, Baak R, Babic N, Bettinotti M, Buller A, Butz K, Campbell M, Civalier C, El-Badry A, Farkas DH, Lyon E, Mandal S, McKinney J, Muralidharan K, Noll L, Sander T, Shabbeer J, Smith C, Telatar M, Toji L, Vairavan A, Vance C, Weck KE, Wu AH, Yeo KT, Zeller M, and Kalman L., Characterization of 107 Genomic DNA Reference Materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1 J Mol Diagn12(6):835-46 2010 |
| PubMed ID: 20889555 |
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| Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA, Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol41(1):90-6 2003 |
| PubMed ID: 12517831 |
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| Bach G, Moskowitz SM, Tieu PT, Matynia A, Neufeld EF, Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area American journal of human genetics53:330-8 1993 |
| PubMed ID: 8328452 |
| Gene Cards |
CYP2C19 |
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CYP2C9 |
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CYP2D6 |
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IDUA |
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UGT1A1 |
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VKORC1 |
| Gene Ontology |
GO:0003940 L-iduronidase activity |
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GO:0004497 monooxygenase activity |
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GO:0005764 lysosome |
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GO:0005783 endoplasmic reticulum |
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GO:0005792 microsome |
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GO:0005984 disaccharide metabolism |
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GO:0006118 electron transport |
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GO:0006789 bilirubin conjugation |
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GO:0007586 digestion |
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GO:0008152 metabolism |
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GO:0008210 estrogen metabolism |
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GO:0015020 glucuronosyltransferase activity |
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GO:0016020 membrane |
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GO:0016021 integral to membrane |
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GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen |
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GO:0018676 (S)-limonene 7-monooxygenase activity |
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GO:0019825 oxygen binding |
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GO:0030203 glycosaminoglycan metabolism |
| NCBI Gene |
Gene ID:1557 |
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Gene ID:1559 |
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Gene ID:1565 |
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Gene ID:3425 |
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Gene ID:54658 |
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Gene ID:79001 |
| NCBI GTR |
124020 CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 19; CYP2C19 |
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124030 CYTOCHROME P450, SUBFAMILY IID, POLYPEPTIDE 6; CYP2D6 |
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191740 UDP-GLYCOSYLTRANSFERASE 1 FAMILY, POLYPEPTIDE A1; UGT1A1 |
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252800 ALPHA-L-IDURONIDASE; IDUA |
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601130 CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9 |
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607015 HURLER-SCHEIE SYNDROME |
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608547 VITAMIN K EPOXIDE REDUCTASE COMPLEX, SUBUNIT 1; VKORC1 |
| OMIM |
124020 CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 19; CYP2C19 |
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124030 CYTOCHROME P450, SUBFAMILY IID, POLYPEPTIDE 6; CYP2D6 |
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191740 UDP-GLYCOSYLTRANSFERASE 1 FAMILY, POLYPEPTIDE A1; UGT1A1 |
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252800 ALPHA-L-IDURONIDASE; IDUA |
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601130 CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9 |
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607015 HURLER-SCHEIE SYNDROME |
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608547 VITAMIN K EPOXIDE REDUCTASE COMPLEX, SUBUNIT 1; VKORC1 |
| Omim Description |
HURLER-SCHEIE SYNDROME |
| Passage Frozen |
9 |
| Split Ratio |
1:4 |
| 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 |
| Supplement |
- |
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