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Fig. 1 | Orphanet Journal of Rare Diseases

Fig. 1

From: Transcript, protein, metabolite and cellular studies in skin fibroblasts demonstrate variable pathogenic impacts of NPC1 mutations

Fig. 1

aNPC1 promoter haplotype variants and respective luciferase reporter activities in %. Reporter activity of pGL3 basic vector was 0.1 ± 0.1% of Haplotype 1 construct activity. Haplotype 3 is present in controls only. b Immunoreactive NPC1 protein in skin fibroblast lines (Western blotting). The cell line numbers and phenotypes are indicated on the top. Equal amount of protein (8 μg) was applied per line. Abnormal banding associated with p.Y276H is indicated by arrowheads. CCD data were used for the quantification. c The mutations are depicted using crystal structure of NPC1 protein 3JD8 [40] and the domains are color-coded according to Li [11]. A schematic of primary structure of the mature NPC1 protein is shown below the structure - domain color coding. NTD – N-terminal domain, TM – transmembrane domain, MLD - middle luminal domain, SSD – sterol sensing domain. The most severe mutations are indicated in bold font. Most of the mutations are in lumenal domains I and C (color-coded circles beside the mutation labels). d Representative images of human skin fibroblasts of a control and patients with selected forms of the disease. 1st column: direct filipin stained cultures. 2nd column: confocal microscopy images anti-NPC1 signal. 3rd column: merge of anti-LAMP2 (red) and anti-NPC1 (green) signal, 4th column: co-localization overlay maps. Values 0 - 1 of the pixels are displayed using lookup table LUT 0–1. All images were processed equally

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