Extended Data Fig. 7: Transcriptional effects of MOF heterozygous de novo mutations.

a-c, RNA-seq analysis of HDFs from MOF syndrome patients, T5 (a), T6 (b) and T8 (c) (n = 4 technical replicates). Volcano plots show all detected transcripts, with vertical dashed lines indicating the Log₂ FC cutoff (calculated by Wald Tests). All detected transcripts belonging to human Mitocarta 3.0 protein transcripts are highlighted in blue. d, Bubble plots show summarized biological processes affected by transcriptional downregulation in T5, T6 and T8 HDFs. Size of bubbles depicts the number of terms belonging to the summary term whereas the color shows their Log₁₀ p-value. The position of the term signifies their relation in semantic space. The 10 most affected processes are listed below each plot. e, Upset plots show overlap of differentially downregulated (upper) and upregulated (lower) amongst T5, T6 and T8 HDFs. Number of overlapping genes are indicated in the panel. f, Oxygen Consumption Rate (OCR) in control, T5 and T6 HDFs measured by sequential treatment with indicated drugs (mean ± s.e.m., n = 9-38 independent samples, two-tailed Student’s t-test was performed on the first time point of basal respiration and on the first time point of respiration following FCCP injection and was calculated using. ****p-value < 0.0001, ***p-value < 0.001, **p-value < 0.01. g, Metabolite analysis in control, T5, T6 and T8. Data is normalized to total protein content (mean fold change ± s.e.m., n = 5 independent experiments, one-way ANOVA followed by Dunnet’s multiple comparison). h, i, OCR with sequential indicated treatments. BJ, control and T5 fibroblasts shows similar levels of complex IV activity (h). T6 and T8 HDFs show lower complex IV activity as compared to the control BJ cells (i). BJ fibroblasts from ATCC were used as an independent control to complement complex IV activity of the HDFs (mean ± s.e.m., n = 3-9 independent samples).

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