Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study

Peter Bauer, David J Balding, Hans H Klünemann, David E J Linden, Daniel S Ory, Mercè Pineda, Josef Priller, Frederic Sedel, Audrey Muller, Harbajan Chadha-Boreham, Richard W D Welford, Daniel S Strasser, Marc C Patterson

Research output: Contribution to journalArticlepeer-review


Niemann-Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either the NPC1 gene (in 95% of cases) or the NPC2 gene. This observational, multicentre genetic screening study evaluated the frequency and phenotypes of NP-C in consecutive adult patients with neurological and psychiatric symptoms. Diagnostic testing for NP-C involved NPC1 and NPC2 exonic gene sequencing and gene dosage analysis. When available, results of filipin staining, plasma cholestane-3β,5α,6β-triol assays and measurements of relevant sphingolipids were also collected. NPC1 and NPC2 gene sequencing was completed in 250/256 patients from 30 psychiatric and neurological reference centres across the EU and USA [median (range) age 38 (18-90) years]. Three patients had a confirmed diagnosis of NP-C; two based on gene sequencing alone (two known causal disease alleles) and one based on gene sequencing and positive filipin staining. A further 12 patients displayed either single mutant NP-C alleles (8 with NPC1 mutations and 3 with NPC2 mutations) or a known causal disease mutation and an unclassified NPC1 allele variant (1 patient). Notably, high plasma cholestane-3β,5α,6β-triol levels were observed for all NP-C cases (n = 3). Overall, the frequency of NP-C patients in this study [1.2% (95% CI; 0.3%, 3.5%)] suggests that there may be an underdiagnosed pool of NP-C patients among adults who share common neurological and psychiatric symptoms.

Original languageEnglish
Pages (from-to)4349-56
Number of pages8
JournalHuman Molecular Genetics
Issue number21
Publication statusE-pub ahead of print - 16 Jun 2013


  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Carrier Proteins
  • Female
  • Genetic Testing
  • Genetic Variation
  • Genotype
  • Glycoproteins
  • Humans
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • Mutation
  • Niemann-Pick Disease, Type C
  • Phenotype
  • Sequence Analysis, DNA
  • Young Adult
  • Journal Article
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't


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