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.
This review will focus on the role of ASM in membrane biology, with a specific emphasis on what a rare genetic disorder (NPD) has taught us about more common events.
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.
The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients.
Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid sphingomyelinase (aSMase) and the resulting accumulation of sphingomyelin in tissues.
The Niemann-Pick disease group is now divided into two distinct entities: (1) acid sphingomyelinase-deficient Niemann-Pick disease (ASM-deficient NPD) resulting from mutations in the SMPD1 gene and encompassing type A and type B as well as intermediate forms; (2) Niemann-Pick disease type C (NP-C) including also type D, resulting from mutations in either the NPC1 or the NPC2 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.
Niemann-Pick disease (NPD) type B is a rare autosomal recessive disease characterized by variable levels of impairment in sphingomyelin phosphodiesterase 1 (SMPD1) activity.
Pulmonary delivery of recombinant acid sphingomyelinase improves clearance of lysosomal sphingomyelin from the lungs of a murine model of Niemann-Pick disease.
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 further developed a computer assisted, three-dimensional model of human ASM based on homologies to known proteins, and used this model to map each NPD mutation in relation to putative substrate binding, hydrolysis and zinc-binding domains.
Niemann-Pick disease (NPD), an autosomal recessive disorder resulting from mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is subdivided into the acute, lethal neuronopathic type A, and the chronic visceral type B, explained by the different residual activity levels of acid sphingomyelinase (ASMase).
Recently, the full-length cDNA and genomic sequences encoding ASM have been isolated and the nature of the molecular lesions causing NPD has been investigated.
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.