GM28383
iPSC from Fibroblast
Description:
SCHEIE SYNDROME
ALPHA-L-IDURONIDASE; IDUA
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Protocols |
Protocol PDF |
|
Biopsy Source
|
Skin
|
|
Cell Type
|
Stem cell
|
|
Cell Subtype
|
Induced pluripotent stem cell
|
|
Transformant
|
Reprogrammed (Sendai)
|
|
Sample Source
|
iPSC from Fibroblast
|
|
Race
|
White
|
|
Country of Origin
|
USA
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Molecular characterization after cell line submission to CCR
|
|
ISCN
|
46,XY[20]
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| Passage Frozen |
16 |
| |
| Induced Pluripotent Stem Cell |
The frozen cell line submitted to the Repository was recovered and expanded. The expanded line was evaluated for viability surface antigen expression and alkaline phosphatase activity. Pluripotency was assessed via embryoid body (EB) formation and PluriTest. Steady-state mRNA expression patterns of undifferentiated iPSC and EBs were determined via real-time PCR. Characterization data are included in the Certificate of Analysis. |
| |
| 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)]. |
| |
| 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 |
Cell line ID: HT142C from parent fibroblast GM01256 - PMID 30052969; 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)]. Researchers purchasing hiPSCs from the NIGMS Repository are responsible for any limited use label licenses (LULLs) applicable to the cell line purchased. The applicable LULL to this line is Sendai-CytoTune. |
| 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 |
| Passage Frozen |
16 |
| Split Ratio |
1:12 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
mTeSR1 |
| Serum |
0% none |
| Substrate |
Matrigel |
| Supplement |
- |
|