Niemann-Pick disease (NPD) is a hereditary lysosomal storage disorder in which mutations in the sphingomyelin phosphodiesterase gene leads to partial or complete deficiency of the sphingomyelinase enzyme.
Recently, a missense mutation in the ASM gene (designated R496L) was detected in more than 30% of the ASM alleles from Ashkenazi Jewish type A NPD patients.
A novel point mutation in the lysosomal acid sphingomyelinase gene has been identified in the recently reported Serbian family with a clinically and biochemically atypical intermediate form of Niemann-Pick disease.
To characterize the mutations causing NPD in Japanese population, we analyzed the genomic sequence of ASM from a Japanese patient with type A NPD by PCR amplification and sequencing.A new mutation, Y446C, was identified.
Following Brady's discovery of the defect in acid sphingomyelinase in Niemann-Pick disease, types A and B, Peter Pentchev, a senior scientist in the group, launched a series of investigations of an unusual lipid storage disease in a spontaneous mouse model.
In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis.
To date, two distinct sphingomyelinases, a lysosomal acid sphingomyelinase (ASM), which is deficient in patients affected with types A and B Niemann-Pick disease (NPD), and a neutral, magnesium-dependent sphingomyelinase (NSM), are candidate enzymes which respond to apoptotic stimulations and cause sphingomyelin hydrolysis and subsequent ceramide generation.
Transient expression of the fsL178, L261X, and M382I mutations in COS-1 cells demonstrated that these lesions did not produce catalytically active ASM, consistent with the severe neuronopathic Type A NPD phenotype.
Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation of undegraded lipids in cells of the viscera and CNS.
MRI was performed in two siblings with the neuropathic sphingomyelinase deficiency caused by identical mixed heterozygosity in the structural acid sphingomyelinase gene.
A novel single base pair deletion in the acid sphingomyelinase (ASM) gene (677delT in the cDNA) was identified in 12 Israeli Arab families with Niemann-Pick disease (NPD) type A.
PCR primers were designed to amplify the repeat region and over 700 normal and NPDASM alleles were analyzed among Ashkenazi Jewish and non-Jewish populations.
We present a case of a 9-month infant with clinical manifestations intermediate between types A and B NPD and genetically illustrating a novel R542X mutation in the exon 6 of SMPD1.
Comprehensive Evaluation of Plasma 7-Ketocholesterol and Cholestan-3β,5α,6β-Triol in an Italian Cohort of Patients Affected by Niemann-Pick Disease due to NPC1 and SMPD1 Mutations.
Inactivating mutations in the SMPD1 gene result in Niemann-Pick diseases type A and B characterized by sphingomyelin accumulation and severely disturbed tissue homeostasis.