期刊
JOURNAL OF CLINICAL LIPIDOLOGY
卷 6, 期 1, 页码 74-80出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2011.08.009
关键词
Acid sphingomyelinase; Cholesterol efflux; High-density lipoprotein cholesterol; Sphingomyelin; Type B Niemann-Pick disease
BACKGROUND: Type A or B Niemann-Pick disease (NPD) is characterized by the accumulation of sphingomyelin in the lysosomes and cell membranes. This accumulation results because of a mutation in the sphingomyelin phosphodiesterase-1 (SMPD-1) gene that causes a deficit in the acid sphingomyelinase (ASM). OBJECTIVE: Herein, we report on a new point mutation in the SMPD-1 gene that was discovered in a patient with type B NPD. METHODS AND RESULTS: A culture of the patient's fibroblasts demonstrated that the observed clinical symptoms and reduced plasma high-density lipoprotein cholesterol (HDL-C) were associated with a reduced efflux of cholesterol. Examination of the skin fibroblasts demonstrated that ASM activity was reduced to approximately 60% of that observed in control cells, and a newly identified point mutation was found in codon 494 [Gly (GGT) -> Cys (TGT)] in the SMPD-1 gene. Furthermore, repeated measurements of the plasma HDL-C levels remained low (17.5-20.5 mg/dL), and the Apo A-I- or HDL-mediated cholesterol efflux from the patient's fibroblasts was significantly reduced as compared with control fibroblasts. CONCLUSION: In summary, we identified a unique point mutation in a patient with type B NPD that was associated with various clinical findings, including a low plasma HDL-C level. This reduced cellular cholesterol efflux may be implicated, at least in part, in low plasma HDL levels. (C) 2012 National Lipid Association. All rights reserved.
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