NA03252
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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White
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Relation to Proband
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proband
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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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| Passage Frozen |
6 |
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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; 2% 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. |
| Remarks |
2% of normal sphingomyelinase activity and deficient phospholipase C activity in fibroblasts; similarly affected brother; type B; donor is a compound heterozygote: one allele with a T>C transition at nucleotide 905 in exon 2 of the SMPD1 gene [905T>C] resulting in a substitution of proline for leucine at codon 302 [Leu302Pro (L302P)]; other allele carries an uncharacterized mutation.
Submission previously diagnosed as Neimann-Pick Disease, Type B; further genetic testing confirmed Niemann-Pick Disease, Type A mutation.
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| Baskfield A, Li R, Beers J, Zou J, Liu C, Zheng W, An induced pluripotent stem cell line (TRNDi009-C) from a Niemann-Pick disease type A patient carrying a heterozygous pL302P (c905 T>C) mutation in the SMPD1 gene Stem cell research38:101461 2019 |
| PubMed ID: 31132580 |
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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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| 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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| Takada G, Satoh W, Komatsu K, Konn Y, Miura Y, Uesaka Y, Transitory type of sphingomyelinase deficient Niemann-Pick disease: clinical and morphological studies and follow-up of two sisters. Tohoku J Exp Med153:27-36 1987 |
| PubMed ID: 2823414 |
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| Pentchev PG, Comly ME, Kruth HS, Patel S, Proestel M, Weintroub H, The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem261:2772-7 1986 |
| PubMed ID: 3949747 |
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| Beaudet AL, Manschreck AA, Metabolism of sphingomyelin by intact cultured fibroblasts: differentiation of Niemann-Pick disease type A and B. Biochem Biophys Res Commun105:14-9 1982 |
| PubMed ID: 7092849 |
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