Description:
NIEMANN-PICK DISEASE, TYPE B
SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1
GLUCOSIDASE, ACID BETA; GBA
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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 |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Ethnicity
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ASHKENAZI
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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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| MUTATION VERIFICATION |
The R496L gene mutation in this sample has been verified by 6 laboratories and the delR608 and N370S mutations have been verified by 5 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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
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| Gene |
SMPD1 |
| Chromosomal Location |
11p15.4-p15.1 |
| Allelic Variant 1 |
607608.0001; NIEMANN-PICK DISEASE, TYPE A |
| Identified Mutation |
ARG496LEU; Levran et al. [Proc. Nat. Acad. Sci. USA 88: 3748-3752 (1991)] used polymerase chain reaction (PCR) to amplify the coding region from the acid sphingomyelinase gene from an Ashkenazi Jewish type A patient. Sequence analysis revealed a single G-to-T change at nucleotide 1487 (in a CpG dinucleotide), predicting an arginine-to-leucine amino acid substitution in residue 496. |
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| Gene |
GBA |
| Chromosomal Location |
1q21 |
| Allelic Variant 1 |
606463.0003; GAUCHER DISEASE, TYPE I |
| Identified Mutation |
ASN370SER; By nucleotide sequence analysis of a genomic clone from an Ashkenazi Jewish patient with type I, Tsuji et al. [Proc. Nat. Acad. Sci. 85: 2349-2352 (1988] found a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change resulted in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. This mutation [1226G (N370S)] accounts for approximately 70% of mutations in the Jewish population. |
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| Gene |
SMPD1 |
| Chromosomal Location |
11p15.4-p15.1 |
| Allelic Variant 2 |
607608.0002; NIEMANN-PICK DISEASE, TYPE B |
| Identified Mutation |
ARG608DEL; In an Ashkenazi Jewish type B patient, Levran et al. [Proc. Nat. Acad. Sci. USA 88: 3748-3752 (1991)] identified a 3-base deletion of nucleotides 1821-1823 which predicted the removal of an arginine residue from position 608 of the acid sphingomyelinase polypeptide. The other cDNA clone from this patient had the R496L mutation previously identified in type A Niemann-Pick disease patients (257200.0001). |
| Remarks |
Clinically affected; organomegaly; lung involvement; neurologically normal; Type B; acid sphingomyelinase enzyme levels < 2% of control; the donor subject is a compound heterozygote; one allele carries a G-to-T change at nucleotide 1487 (in a CpG dinucleotide) of the SPMD1 gene which results in an arginine-to-leucine amino acid substitution in residue 496 [Arg496Leu (R496L)]; the second allele carries a 3-base deletion of nucleotides 1821-1823 which removes an arginine residue from position 608 (Arg608DEL); donor subject is also heterozygous for an A>G transition at nucleotide 1226 in exon 9 of the GBA gene (1226A>G) resulting in a substitution of serine for asparagine at codon 370 [Asn370Ser (N370S)] [codons are numbered from the first codon of the mature protein; the cDNA is numbered from the first initiating AUG]
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| Barbara Canonico, Erica Cesarini, Sara Salucci, Francesca Luchetti, Elisabetta Falcieri, Gianna Di Sario, Fulvio Palma, and Stefano Papa1., Defective Autophagy, Mitochondrial Clearance and Lipophagy in Niemann-Pick Type B Lymphocytes. Plos One11(10):e0165780 2016 |
| PubMed ID: 27798705 |
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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 |
| dbSNP |
dbSNP ID: 12321 |
| Gene Cards |
GBA |
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SMPD1 |
| Gene Ontology |
GO:0004348 glucosylceramidase activity |
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GO:0004767 sphingomyelin phosphodiesterase activity |
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GO:0005764 lysosome |
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GO:0005975 carbohydrate metabolism |
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GO:0006665 sphingolipid metabolism |
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GO:0006685 sphingomyelin catabolism |
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GO:0007040 lysosome organization and biogenesis |
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GO:0007165 signal transduction |
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GO:0007399 neurogenesis |
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GO:0016020 membrane |
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GO:0016798 hydrolase activity, acting on glycosyl bonds |
| NCBI Gene |
Gene ID:2629 |
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Gene ID:6609 |
| NCBI GTR |
606463 GLUCOSIDASE, BETA, ACID; GBA |
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607608 SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1 |
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607616 NIEMANN-PICK DISEASE, TYPE B |
| OMIM |
606463 GLUCOSIDASE, BETA, ACID; GBA |
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607608 SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1 |
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607616 NIEMANN-PICK DISEASE, TYPE B |
| Omim Description |
NIEMANN-PICK DISEASE, TYPE B |
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