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Zeiger WA, Jamal NI, Scheuner MT, et al. Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing. JIMD Rep. 2018;41:47-51doi: 10.1007/8904_2018_90.
Zeiger, W. A., Jamal, N. I., Scheuner, M. T., Pittman, P., Raymond, K. M., Morra, M., & Mishra, S. K. (2018). Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing. JIMD reports, 4147-51. https://doi.org/10.1007/8904_2018_90
Zeiger, William A, et al. "Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing." JIMD reports vol. 41 (2018): 47-51. doi: https://doi.org/10.1007/8904_2018_90
Zeiger WA, Jamal NI, Scheuner MT, Pittman P, Raymond KM, Morra M, Mishra SK. Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing. JIMD Rep. 2018;41:47-51. doi: 10.1007/8904_2018_90. Epub 2018 Feb 17. PMID: 29453517; PMCID: PMC6122056.
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JIMD Rep. 2018;41:47-51. doi: 10.1007/8904_2018_90. Epub 2018 Feb 17.

Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing.

JIMD reports

William A Zeiger, Nasheed I Jamal, Maren T Scheuner, Patricia Pittman, Kimiyo M Raymond, Massimo Morra, Shri K Mishra

Affiliations

  1. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. [email protected].
  2. Department of Neurology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. [email protected].
  3. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
  4. Department of Neurology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
  5. Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
  6. Department of Medical Genetics, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
  7. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
  8. Personalis Inc., Menlo Park, CA, USA.
  9. Department of Neurology, USC Keck School of Medicine, Los Angeles, CA, USA.
  10. Department of Neurology, Olive View-UCLA Medical Center, Sylmar, CA, USA.

PMID: 29453517 PMCID: PMC6122056 DOI: 10.1007/8904_2018_90

Abstract

Here, we present a case of a 31-year-old man with progressive cognitive decline, ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic studies over the course of several years failed to yield a diagnosis. Initial whole exome sequencing through a commercial laboratory identified several variants of uncertain significance; however, follow-up clinical examination and testing ruled each of these out. Eventually, repeat whole exome sequencing identified a known pathogenic intronic variant in the NPC1 gene (NM_000271.4, c.1554-1009G>A) and an additional heterozygous exonic variant of uncertain significance in the NPC1 gene (NM_000271.4, c.2524T>C). Follow-up biochemical testing was consistent with a diagnosis of probable Niemann-Pick disease Type C (NP-C). This case illustrates the potential of whole exome sequencing for diagnosing rare complex neurologic diseases. It also identifies several potential common pitfalls that must be navigated by clinicians when interpreting commercial whole exome sequencing results.

Keywords: Ataxia; Dementia; Dystonia; Metabolic disease; Neurodegeneration; Niemann–Pick type C; Whole exome sequencing

References

  1. JAMA Neurol. 2014 Oct;71(10):1237-46 - PubMed
  2. Orphanet J Rare Dis. 2014 Nov 26;9:176 - PubMed
  3. Hum Mutat. 2009 Nov;30(11):E993-E1001 - PubMed
  4. Neurol Clin Pract. 2017 Dec;7(6):499-511 - PubMed
  5. Neurology. 2012 May 15;78(20):1560-7 - PubMed
  6. Mol Genet Metab. 2016 Aug;118(4):244-54 - PubMed
  7. Methods Cell Biol. 2015;126:357-75 - PubMed
  8. Orphanet J Rare Dis. 2013 Oct 17;8:166 - PubMed
  9. Diabetes. 2017 Apr;66(4):935-947 - PubMed
  10. J Lipid Res. 2010 Feb;51(2):406-15 - PubMed

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