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Case Reports
. 2017 Sep 1;3(5):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

Amber Hildreth  1   2 , Kristen Wigby  3 , Shimul Chowdhury  1 , Shareef Nahas  1 , Jaime Barea  3 , Paulina Ordonez  2   4 , Sergey Batalov  1 , David Dimmock  1 , Stephen Kingsmore  1 ; RCIGM Investigators
Affiliations
Case Reports

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

Amber Hildreth et al. Cold Spring Harb Mol Case Stud. .

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.

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References

    1. Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, et al. 1997. Niemann–Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277: 228–231. - PubMed
    1. Coonrod EM, Margraf RL, Russell A, Voelkerding KV, Reese MG. 2013. Clinical analysis of genome next-generation sequencing data using the Omicia platform. Expert Rev Mol Diagn 13: 529–540. - PMC - PubMed
    1. Degtyareva AV, Mikhailova SV, Zakharova EY, Tumanova EL, Puchkova AA. 2016. Visceral symptoms as a key diagnostic sign for the early infantile form of Niemann–Pick disease type C in a Russian patient: a case report. J Med Case Rep 10: 143. - PMC - PubMed
    1. Di Rocco M, Dardis A, Madeo A, Barone R, Fiumara A. 2012. Early miglustat therapy in infantile Niemann–Pick disease type C. Pediatr Neurol 47: 40–43. - PubMed
    1. Fernandez-Valero EM, Ballart A, Iturriaga C, Lluch M, Macias J, Vanier MT, Pineda M, Coll MJ. 2005. Identification of 25 new mutations in 40 unrelated Spanish Niemann–Pick type C patients: genotype–phenotype correlations. Clin Genet 68: 245–254. - PubMed

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