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

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.

Author information

1
Rady Children's Institute of Genomic Medicine, San Diego, California 92123, USA.
2
Department of Pediatrics, Division of Gastroenterology, University of California San Diego, La Jolla, California 92093, USA.
3
Department of Pediatrics, Division of Medical Genetics, University of California San Diego, La Jolla, California 92093, USA.
4
Sanford Consortium of Regenerative Medicine, La Jolla, California 92037, USA.

Abstract

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

PMID:
28550066
PMCID:
PMC5593156
DOI:
10.1101/mcs.a001966
[Indexed for MEDLINE]
Free PMC Article

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