Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine
Journal
npj Genomic Medicine
ISSN
2056-7944
Date Issued
2023
Author(s)
Macarena Las Heras
Benjamín Szenfeld
Rami A. Ballout
Emanuele Buratti
Silvana Zanlungo
Andrea Dardis
Andrés D. Klein
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:p>Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the <jats:italic>NPC1</jats:italic> and <jats:italic>NPC2</jats:italic> genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. This article reviews the phenotypic variation of NPC and discusses its possible causes, such as the remaining function of the defective protein, modifier genes, sex, environmental cues, and splicing factors, among others. We propose that these factors should be considered when designing or repurposing treatments for this disease. Despite its seeming complexity, this proposition is not far-fetched, considering the expanding interest in precision medicine and easier access to multi-omics technologies.</jats:p>
Cite this document
Las Heras, M., Szenfeld, B., Ballout, R. A., Buratti, E., Zanlungo, S., Dardis, A., & Klein, A. D. (2023). Understanding the phenotypic variability in Niemann-Pick disease type C (Npc): A need for precision medicine. Npj Genomic Medicine, 8(1), 21. https://doi.org/10.1038/s41525-023-00365-w
Subjects
2 hydroxypropyl beta cyclodextrin
;
abelson kinase
;
arimoclomol
;
biological marker
;
calcium channel
;
calcium ion
;
cholesterol
;
messenger rna
;
miglustat
;
n acetylleucine
;
npc intracellular cholesterol transporter 1
;
protein tyrosine kinase inhibitor
;
rna splicing factor
;
sirolimus
;
vorinostat
;
allele
;
central nervous system
;
cholesterol transport
;
clinical trial (topic)
;
degenerative disease
;
disease exacerbation
;
disease severity
;
endolysosome
;
environmental factor
;
family
;
gene mapping
;
gene mutation
;
genetic background
;
genetic variability
;
genotype phenotype correlation
;
hepatosplenomegaly
;
human
;
juvenile
;
loss of function mutation
;
lysosome
;
modifier gene
;
multiomics
;
neurologic disease
;
newborn disease
;
newborn jaundice
;
niemann pick disease
;
nonhuman
;
onset age
;
personalized medicine
;
pharmacogenomics
;
phenotype
;
phenotypic variation
;
review
;
risk factor
;
rna processing
;
rna splicing
;
sex difference
;
splenomegaly
;
symptom
;
treatment response