Description:
NIEMANN-PICK DISEASE, TYPE A
SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1
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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 Lipid Metabolism |
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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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ASHKENAZI
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Molecular characterization before 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 |
6.53 |
| Passage Frozen |
2 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| sphingomyelin phosphodiesterase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.4.12; <1% activity. |
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| Gene |
SMPD1 |
| Chromosomal Location |
11p15.4-p15.1 |
| Allelic Variant 1 |
607608.0010; NIEMANN-PICK DISEASE, TYPE A |
| Identified Mutation |
LEU302PRO; Levran et al. (Blood 80: 2081-2087, 1992) reported a T-to-C transition at nucleotide 905, predicting a leucine-to-proline substitution at SMPD1 codon 302 in 8 of 34 (23.5%) Ashkenazi type A Niemann-Pick disease (257200) alleles studied. In contrast, it was not found in any of the SMPD1 alleles from non-Jewish type A patients or in alleles from type B patients or in 100 SMPD1 alleles from normal Ashkenazi Jewish persons. Three mutations, R496L (607608.0001), 1-BP DEL, PRO330FS (607608.0011), and this mutation, account for about 65% of the mutant SMPD1 alleles in Ashkenazi Jewish type A Niemann-Pick disease patients. |
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| Gene |
SMPD1 |
| Chromosomal Location |
11p15.4-p15.1 |
| Allelic Variant 2 |
607608.0010; NIEMANN-PICK DISEASE, TYPE A |
| Identified Mutation |
LEU302PRO; Levran et al. (Blood 80: 2081-2087, 1992) reported a T-to-C transition at nucleotide 905, predicting a leucine-to-proline substitution at SMPD1 codon 302 in 8 of 34 (23.5%) Ashkenazi type A Niemann-Pick disease (257200) alleles studied. In contrast, it was not found in any of the SMPD1 alleles from non-Jewish type A patients or in alleles from type B patients or in 100 SMPD1 alleles from normal Ashkenazi Jewish persons. Three mutations, R496L (607608.0001), 1-BP DEL, PRO330FS (607608.0011), and this mutation, account for about 65% of the mutant SMPD1 alleles in Ashkenazi Jewish type A Niemann-Pick disease patients. |
| Remarks |
Clinically affected; organomegaly; neurological involvement; deceased; Type A; acid sphingomyelinase enzyme levels <1% of controls; the donor subject is homozygous for a T-to-C transition at nucleotide 905 (CTT>CCT) of the SPMD1 gene, resulting in a leucine-to-proline substitution at codon 302 [LEU302PRO (L302P)]; same subject as GM27463 (iPSC). |
| , CORRIGENDUM Stem cells translational medicine10:1360 2021 |
| PubMed ID: 34310862 |
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| Newcomb B1, Rhein C1,2, Mileva I1, Ahmad R3, Clarke CJ1, Snider J1, Obeid LM1,4, Hannun YA, Identification of an acid sphingomyelinase ceramide kinase pathway in the regulation of the chemokine CCL5 Journal of Lipid Research59:1219-1229 2018 |
| PubMed ID: 29724781 |
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| Long Y, Xu M, Li R, Dai S, Beers J, Chen G, Soheilian F, Baxa U, Wang M, Marugan JJ, Muro S, Li Z, Brady R, Zheng W, Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A Stem cells translational medicine5:1644-1655 2015 |
| PubMed ID: 27484861 |
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| 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 |
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| Xu M1, Liu K, Swaroop M, Porter FD, Sidhu R, Firnkes S, Ory DS, Marugan JJ, Xiao J, Southall N, Pavan WJ, Davidson C, Walkley SU, Remaley AT, Baxa U, Sun W, McKew JC, Austin CP, Zheng W., δ-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders. J Biol Chem287(47):39349-60 2012 |
| PubMed ID: 23035117 |
| Passage Frozen |
2 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
10% |
| Medium |
Dulbecco Modified Eagles Medium (high glucose) with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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