Nephropathic cystinosis is a rare, inherited metabolic disease caused by 
functional defects of cystinosin associated with mutations in the CTNS gene. The 
mechanisms underlying the phenotypic alterations associated with this disease 
are not well known. In this study, gene expression profiles in peripheral blood 
of nephropathic cystinosis patients (N = 7) were compared with controls (N = 7) 
using microarray technology. In unsupervised hierarchical clustering analysis, 
cystinosis samples co-clustered, and 1,604 genes were significantly 
differentially expressed between both groups. Gene ontology analysis revealed 
that differentially expressed genes in cystinosis were enriched in cell 
organelles such as mitochondria, lysosomes, and endoplasmic reticulum (p ≤ 
0.030). The majority of the differentially regulated genes were involved in 
oxidative phosphorylation, apoptosis, mitochondrial dysfunction, endoplasmic 
reticulum stress, antigen processing and presentation, B-cell-receptor 
signaling, and oxidative stress (p ≤ 0.003). Validation of selected genes 
involved in apoptosis and oxidative phosphorylation was performed by 
quantitative real-time polymerase chain reaction (PCR). Electron microscopy and 
confocal imaging of cystinotic renal proximal tubular epithelial cells further 
confirmed anomalies in the cellular organelles and pathways identified by 
microarray analysis. Further analysis of these genes and pathways may offer 
critical insights into the clinical spectrum of cystinosis patients and 
ultimately lead to novel links for targeted therapy.