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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JEWISH
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Relation to Proband
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parent
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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase 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; 20% 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; clinically unaffected; positive family history; about 20% of normal sphingomyelinase activity and increased cholesterol biosynthesis in fibroblasts; parent of a child with type A; proband not in Repository; donor subject is heterozygous for a deletion of a single cytosine in exon 2 at codon 330 [990delC (which normally encodes a proline residue)] resulting in a frameshift leading to the formation of a premature stop (TGA) at codon 382 (1-BP DEL, Pro330FS) of the SMPD1 gene. |
| Levran O, Desnick RJ, Schuchman EH, Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients. Proc Natl Acad Sci U S A88:3748-52 1991 |
| PubMed ID: 2023926 |
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| Maziere JC, Maziere C, Gardette J, Mora L, Polonovski J, Changes in cholesterol metabolism in cultured fibroblasts from patients with Niemann-Pick disease. Biochem Biophys Res Commun102:113-8 1981 |
| PubMed ID: 6272787 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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