GM03252

GM03252 Fibroblast

Description:

NIEMANN-PICK DISEASE, TYPE A
SPHINGOMYELIN PHOSPHODIESTERASE 1, ACID LYSOSOMAL; SMPD1

Affected:

Yes

Sex:

Female

Age:

21 FW (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples

Class

Disorders of Lipid Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

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.

Characterizations

Passage Frozen

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; 2% 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.

Phenotypic Data

Remarks

Publications

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

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

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