Rapid whole-genome sequencing identifies a novel homozygous NPC1 variant associated with Niemann-Pick type C1 disease in a 7-week-old male with cholestasis

Cold Spring Harb Mol Case Stud. 2017 Sep 1;3(5):a001966. doi: 10.1101/mcs.a001966. Print 2017 Sep.


Niemann-Pick type C disease (NPC; OMIM #257220) is an inborn error of intracellular cholesterol trafficking. It is an autosomal recessive disorder caused predominantly by mutations in NPC1 Although characterized as a progressive neurological disorder, it can also cause cholestasis and liver dysfunction because of intrahepatocyte lipid accumulation. We report a 7-wk-old infant who was admitted with neonatal cholestasis, and who was diagnosed with a novel homozygous stop-gain variant in NPC1 by rapid whole-genome sequencing (WGS). WGS results were obtained 16 d before return of the standard clinical genetic test results and prompted initiation of targeted therapy.

Keywords: abnormal cholesterol homeostasis; clinodactyly of the 5th finger; foam cells with lamellar inclusion bodies; generalized neonatal hypotonia; hepatosplenomegaly; prolonged neonatal jaundice.

Publication types

  • Case Reports

MeSH terms

  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cholestasis / complications
  • Cholestasis / genetics
  • Cholesterol / genetics
  • Cholesterol / metabolism
  • Genome / genetics
  • Homozygote
  • Humans
  • Infant
  • Liver Diseases / complications
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mutation
  • Niemann-Pick Disease, Type C / complications
  • Niemann-Pick Disease, Type C / diagnosis*
  • Niemann-Pick Disease, Type C / genetics*
  • Niemann-Pick Disease, Type C / metabolism
  • Niemann-Pick Diseases / complications
  • Niemann-Pick Diseases / genetics
  • Sequence Analysis, DNA / methods


  • Carrier Proteins
  • Membrane Glycoproteins
  • NPC1 protein, human
  • Cholesterol