Correlation of age of onset and clinical severity in Niemann–Pick disease type C1 with lysosomal abnormalities and gene expression

Autor: Laura L. Baxter, Dawn E. Watkins-Chow, Nicholas L. Johnson, Nicole Y. Farhat, Frances M. Platt, Ryan K. Dale, Forbes D. Porter, William J. Pavan, Jorge L. Rodriguez-Gil
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-022-06112-y
Popis: Abstract Niemann–Pick disease type C1 (NPC1) is a rare, prematurely fatal lysosomal storage disorder which exhibits highly variable severity and disease progression as well as a wide-ranging age of onset, from perinatal stages to adulthood. This heterogeneity has made it difficult to obtain prompt diagnosis and to predict disease course. In addition, small NPC1 patient sample sizes have been a limiting factor in acquiring genome-wide transcriptome data. In this study, primary fibroblasts from an extensive cohort of 41 NPC1 patients were used to validate our previous findings that the lysosomal quantitative probe LysoTracker can be used as a predictor for age of onset and disease severity. We also examined the correlation between these clinical parameters and RNA expression data from primary fibroblasts and identified a set of genes that were significantly associated with lysosomal defects or age of onset, in particular neurological symptom onset. Hierarchical clustering showed that these genes exhibited distinct expression patterns among patient subgroups. This study is the first to collect transcriptomic data on such a large scale in correlation with clinical and cellular phenotypes, providing a rich genomic resource to address NPC1 clinical heterogeneity and discover potential biomarkers, disease modifiers, or therapeutic targets.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje