NA00112
DNA from Fibroblast
Description:
NIEMANN-PICK DISEASE, TYPE A
SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples |
| Class |
Disorders of Lipid Metabolism |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
|
Cell Type
|
Fibroblast
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
DNA from Fibroblast
|
|
Race
|
White
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| PDL at Freeze |
6.27 |
| Passage Frozen |
9 |
| |
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
| |
| MUTATION VERIFICATION |
The gene mutation(s) in this sample have been verified by 6 laboratories. |
| |
| sphingomyelin phosphodiesterase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.4.12; 0% activity. |
| |
| 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. |
| |
| 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 |
No detectable sphingomyelinase activity and increased cholesterol biosynthesis in fibroblasts; type A; donor subject is homozygous for 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)].
|
| Scotto Rosato A, Krogsaeter EK, Jaslan D, Abrahamian C, Montefusco S, Soldati C, Spix B, Pizzo MT, Grieco G, Böck J, Wyatt A, Wünkhaus D, Passon M, Stieglitz M, Keller M, Hermey G, Markmann S, Gruber-Schoffnegger D, Cotman S, Johannes L, Crusius D, Boehm U, Wahl-Schott C, Biel M, Bracher F, De Leonibus E, Polishchuk E, Medina DL, Paquet D, Grimm C, TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann-Pick type C1, and Batten disease EMBO molecular medicine14:e15377 2022 |
| PubMed ID: 35929194 |
| |
| 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 disease14:105046 2020 |
| PubMed ID: 32798728 |
| |
| Schultz ML, Fawaz MV, Azaria RD, Hollon TC, Liu EA, Kunkel TJ, Halseth TA, Krus KL, Ming R, Morin EE, McLoughlin HS, Bushart DD, Paulson HL, Shakkottai VG, Orringer DA, Schwendeman AS, Lieberman AP, Synthetic high-density lipoprotein nanoparticles for the treatment of Niemann-Pick diseases BMC medicine17:200 2019 |
| PubMed ID: 31711490 |
| |
| Zhao K, van der Spoel A, Castiglioni C, Gale S, Fujiwara H, Ory DS, Ridgway ND, 19q1312 microdeletion syndrome fibroblasts display abnormal storage of cholesterol and sphingolipids in the endo-lysosomal system Biochimica et biophysica acta1864:2108-2118 2017 |
| PubMed ID: 29580926 |
| |
| 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 |
| |
| 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 |
| |
| Lee CY, Lesimple A, Denis M, Vincent J, Larsen A, Mamer O, Krimbou L, Genest J, Marcil M, Increased sphingomyelin content impairs HDL biogenesis and maturation in human Niemann-Pick disease type B Journal of lipid research47:622-32 2005 |
| PubMed ID: 16319418 |
| |
| Choudhury A, Sharma DK, Marks DL, Pagano RE, ted Endosomal Cholesterol in Niemann-Pick Cells Inhibits Rab4 and Perturbs Membrane Recycling. Mol Biol CellEpub ahead of print:622-32 2004 |
| PubMed ID: 15292453 |
| |
| Lee CY, Krimbou L, Vincent J, Bernard C, Larramée P, Genest J, Marcil M, Compound heterozygosity at the sphingomyelin phosphodiesterase-1 (SMPD1) gene is associated with low HDL cholesterol Human genetics112:552-62 2003 |
| PubMed ID: 12607113 |
| |
| Gamard CJ, Dbaibo GS, Liu B, Obeid LM, Hannun YA, Selective involvement of ceramide in cytokine-induced apoptosis. Ceramide inhibits phorbol ester activation of nuclear factor kappaB. J Biol Chem272(26):16474-81 1997 |
| PubMed ID: 9195956 |
| |
| 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 |
| |
| Koval M, Pagano RE, Sorting of an internalized plasma membrane lipid between recycling and degradative pathways in normal and Niemann-Pick, type A fibroblasts. J Cell Biol111:429-42 1990 |
| PubMed ID: 2380243 |
| |
| Liscum L, Faust JR, The intracellular transport of low density lipoprotein-derived cholesterol is
inhibited in Chinese hamster ovary cells cultured with
3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one. J Biol Chem264(20):11796-806 1989 |
| PubMed ID: 2745416 |
| |
| 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 |
| |
| 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 |
| |
| 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 |
| |
| Maziere JC, Maziere C, Mora L, Routier JD, Polonovski J, In situ degradation of sphingomyelin by cultured normal fibroblasts and fibroblasts from patients with Niemann-Pick disease type A and C. Biochem Biophys Res Commun108:1101-6 1982 |
| PubMed ID: 7181884 |
| |
| Silverstein E, Friedland J, Angiotensin converting enzyme in cultured fibroblasts in Gaucher and Niemann-Pick diseases. Proc Soc Exp Biol Med170:251-3 1982 |
| PubMed ID: 6283559 |
| |
| 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 |
| |
| Beaudet AL, Hampton MS, Patel K, Sparrow JT, Acidic phospholipases in cultured human fibroblasts: deficiency of phospholipase C in Niemann-Pick disease. Clin Chim Acta108:403-14 1980 |
| PubMed ID: 6781796 |
|
|