title: Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C.
abstract: OBJECTIVE
  Niemann-Pick disease type C (NP-C) is an autosomal recessive lipid storage disease manifested by an impairment in cellular cholesterol homeostasis. The clinical phenotype of NP-C is extremely variable, ranging from an acute neonatal form to an adult late-onset presentation. To facilitate phenotype-genotype studies, we have analyzed multiple Israeli NP-C families.
  
  
  METHODS
  The severity of the disease was assessed by the age at onset, hepatic involvement, neurological deterioration, and cholesterol esterification studies. Screening of the entire NPC1 coding sequence allowed for molecular characterization and identification of disease causing mutations.
  
  
  RESULTS
  A total of nine NP-C index cases with mainly neurovisceral involvement were characterized. We demonstrated a possible link between the severity of the clinical phenotype and the cholesterol esterification levels in fibroblast cultures following 24 hours of in vitro cholesterol loading. In addition, we identified eight novel mutations in the NPC1 gene.
  
  
  CONCLUSIONS
  Our results further support the clinical and allelic heterogeneity of NP-C and point to possible association between the clinical and the biochemical phenotype in distinct affected Israeli families.
authors.affiliation: Department of Human Genetics, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: V
authors.initials: V
authors.lastname: Meiner
authors.forename: S
authors.initials: S
authors.lastname: Shpitzen
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: A
authors.initials: A
authors.lastname: Klar
authors.forename: Z
authors.initials: Z
authors.lastname: Ben-Neriah
authors.forename: J
authors.initials: J
authors.lastname: Zlotogora
authors.forename: M
authors.initials: M
authors.lastname: Sagi
authors.forename: A
authors.initials: A
authors.lastname: Lossos
authors.forename: R
authors.initials: R
authors.lastname: Bargal
authors.forename: V
authors.initials: V
authors.lastname: Sury
authors.forename: R
authors.initials: R
authors.lastname: Carmi
authors.forename: E
authors.initials: E
authors.lastname: Leitersdorf
authors.forename: M
authors.initials: M
authors.lastname: Zeigler
mesh_terms: D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism; D003241:Consanguinity; D004951:Esterification; D005347:Fibroblasts; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007557:Israel; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D002784:Cholesterol