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 journalArticle

48 Citations (Scopus)

Abstract

Niemann-Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either theNPC1gene (in95%of cases) or theNPC2gene. 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 5 3). Overall, the frequency of NP-C patients in this study [1.2% (95% CI; 0.3%, 3.5%)] suggests that there maybe an underdiagnosed pool of NP-C patients among adults who share common neurological and psychiatric symptoms.

Original languageEnglish (US)
Article numberddt284
Pages (from-to)4349-4356
Number of pages8
JournalHuman Molecular Genetics
Volume22
Issue number21
DOIs
StatePublished - Nov 2013

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Type C Niemann-Pick Disease
Genetic Testing
Psychiatry
Filipin
Mutation
Alleles
Genes
Staining and Labeling
Sphingolipids
Gene Dosage
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Bauer, P., Balding, D. J., Klünemann, H. H., Linden, D. E. J., Ory, D. S., Pineda, M., ... Patterson, M. C. (2013). Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: Findings from the ZOOM study. Human Molecular Genetics, 22(21), 4349-4356. [ddt284]. https://doi.org/10.1093/hmg/ddt284

Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms : Findings from the ZOOM study. / Bauer, Peter; Balding, David J.; Klünemann, Hans H.; Linden, David E J; Ory, Daniel S.; Pineda, Mercè; Priller, Josef; Sedel, Frederic; Muller, Audrey; Chadha-Boreham, Harbajan; Welford, Richard W D; Strasser, Daniel S.; Patterson, Marc C.

In: Human Molecular Genetics, Vol. 22, No. 21, ddt284, 11.2013, p. 4349-4356.

Research output: Contribution to journalArticle

Bauer, P, Balding, DJ, Klünemann, HH, Linden, DEJ, Ory, DS, Pineda, M, Priller, J, Sedel, F, Muller, A, Chadha-Boreham, H, Welford, RWD, Strasser, DS & Patterson, MC 2013, 'Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: Findings from the ZOOM study', Human Molecular Genetics, vol. 22, no. 21, ddt284, pp. 4349-4356. https://doi.org/10.1093/hmg/ddt284
Bauer, Peter ; Balding, David J. ; Klünemann, Hans H. ; Linden, David E J ; Ory, Daniel S. ; Pineda, Mercè ; Priller, Josef ; Sedel, Frederic ; Muller, Audrey ; Chadha-Boreham, Harbajan ; Welford, Richard W D ; Strasser, Daniel S. ; Patterson, Marc C. / Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms : Findings from the ZOOM study. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 21. pp. 4349-4356.
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