GM16193

GM16193 LCL from B-Lymphocyte

Description:

NIEMANN-PICK DISEASE, TYPE B
SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1
GLUCOSIDASE, ACID BETA; GBA

Affected:

Yes

Sex:

Male

Age:

No Data

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples

Class

Disorders of Lipid Metabolism

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

ASHKENAZI

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

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]

Characterizations

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.

sphingomyelin phosphodiesterase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.4.12; <2% activity.

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

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.

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.

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).

Phenotypic Data

Remarks

Publications

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

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

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