title: Reduced cellular cholesterol efflux and low plasma high-density lipoprotein cholesterol in a patient with type B Niemann-Pick disease because of a novel SMPD-1 mutation.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5-Zaufu-cho, Hirosaki 036-8562, Japan. tmsw@cc.hirosaki-u.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Tamasawa
authors.forename: Shinobu
authors.initials: S
authors.lastname: Takayasu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Maki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Kota
authors.initials: K
authors.lastname: Matsuki
authors.forename: Jutaro
authors.initials: J
authors.lastname: Tanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Jun
authors.initials: J
authors.lastname: Matsui
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suda
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D003110:Colonic Neoplasms / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D003480:Cushing Syndrome / Q000150:complications / Q000175:diagnosis; D005347:Fibroblasts / Q000378:metabolism; D056726:Genetic Association Studies; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D052537:Niemann-Pick Disease, Type B / Q000097:blood / Q000150:complications / Q000235:genetics*; D017354:Point Mutation; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D002784:Cholesterol; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase