NA13205
DNA from Fibroblast
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
GeT-RM Samples |
| Class |
Disorders of Lipid 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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Not Reported
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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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Biochemical 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 |
5.67 |
| Passage Frozen |
9 |
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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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| MUTATION VERIFICATION |
The gene mutation(s) in this sample have been verified by 6 laboratories. |
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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; 0% activity. |
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| Gene |
SMPD1 |
| Chromosomal Location |
11p15.4-p15.1 |
| Allelic Variant 1 |
607608.0011; NIEMANN-PICK DISEASE, TYPE A |
| Identified Mutation |
1-BP DEL, PRO330FS; Levran et al. (Blood 80: 2081-2087, 1992) described a new mutation that causes type A Niemann-Pick disease (257200) in Ashkenazi Jewish patients. Deletion of a single cytosine in codon 330 of the SMPD1 cDNA (which normally encodes a proline residue) caused a frameshift that led to the formation of a premature stop (TGA) at codon 382. Three mutations, R496L (607608.0001), L302P (607608.0010), and this mutation, account for about 65% of the mutant SMPD1 alleles in Ashkenazi Jewish type A Niemann-Pick disease patients. The single base deletion causing the pro330FS mutation was in a region of the gene where 9 of the 10 residues were cytosines. |
| Remarks |
Ashkenazi; developmental delay; hypotonia; does not show marked hepatosplenomegaly; no detectable sphingomyelinase activity in WBC and fibroblasts; donor subject has one allele with a deletion of a single cytosine in exon 2 at codon 330 of the SMPD1 gene [990delC] resulting in a frameshift leading to the formation of a premature stop (TGA) at codon 382 [P330fsX382]. Same subject as GM27464 (iPSC).
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| , CORRIGENDUM Stem cells translational medicine10:1360 2021 |
| PubMed ID: 34310862 |
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| Pascua-Maestro R, Corraliza-Gomez M, Fadrique-Rojo C, Ledesma MD, Schuchman EH, Sanchez D, Ganfornina MD, Apolipoprotein D-mediated preservation of lysosomal function promotes cell survival and delays motor impairment in Niemann-Pick type A disease Neurobiology of disease10:105046 2020 |
| PubMed ID: 32798728 |
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| Yañez MJ, Marín T, Balboa E, Klein AD, Alvarez AR, Zanlungo S, Finding pathogenic commonalities between Niemann-Pick type C and other lysosomal storage disorders: Opportunities for shared therapeutic interventions Biochimica et biophysica acta Molecular basis of disease1866:165875 2020 |
| PubMed ID: 32522631 |
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| Corcelle-Termeau E, Vindeløv SD, Hämälistö S, Mograbi B, Keldsbo A, Bräsen JH, Favaro E, Adam D, Szyniarowski P, Hofman P, Krautwald S, Farkas T, Petersen NH, Rohde M, Linkermann A, Jäättelä M, Excess sphingomyelin disturbs ATG9A trafficking and autophagosome closure Autophagy12:833-49 2016 |
| PubMed ID: 27070082 |
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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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| Kalman L, Wilson JA, Buller A, Dixon J, Edelmann L, Geller L, Highsmith WE, Holtegaard L, Kornreich R, Rohlfs EM, Payeur TL, Sellers T, Toji L, Muralidharan K, Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent The Journal of molecular diagnostics : JMD11:530-6 2009 |
| PubMed ID: 19815695 |
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