Table 1.
Demographic and clinical data of the individuals with 22q11Ds included in the study.
Figure 1.
Diagram of the 22q11.2 deletion region.
Schematic overview of chromosome 22 and the deletion endpoints characterized in the participants of this study using qPCR. Individuals 1 to 29 had a deletion between PRODH and D22S936. One individual had the deletion located between the TUPLE1 and ZNF74 genes. Gene used, order of genes, LCRs A–D, and the common 3 Mb and 1.5 Mb deletion are indicated. Thin black lines indicate deleted region, solid black thick lines indicate chromosomal regions present in two copies, and gray boxes indicate uncertain location of the deletion breakpoints. Each numbered chromosome represents one individual.
Figure 2.
Box plots showing the relative transcript expression levels for six genes mapping within the deleted region and of the GAPDH gene, used as control. Total RNA was isolated from 90 individuals with 22q11DS (22q) and from 40 typical developing age-matched controls (TD). Error bars indicate standard errors. mRNA levels were normalized to the reference Glucuronidase gene. Respective p-values are shown.
Figure 3.
a) box plots showing a decreased DGCR8 mRNA levels in subjects with 22q11DS compared to TD and b) DGCR8 protein expression levels measured by Western blot analysis shows a significant decrease in 22q11DS individuals when compared to TD controls. c) Representative Western blot showing decreased DGCR8 expression.
Figure 4.
Altered miRNA expression in 22q11DS.
Relative miRNA levels are shown for 7 miRNAs that demonstrated differential expression levels when comparing 30 individuals with 22q11DS and 15 TD individuals. miRNA levels were normalized to the reference U6 snRNA. Circles represent observed data. Horizontal lines represent geometric means. Respective p-values are shown.
Figure 5.
Observed correlation between dysregulated miRNAs and left hippocampal volume.
Graphs showing a correlation between miRNA expression levels and left hippocampal volume within the 22q11DS group. Open circles represent individuals with 22q11DS; the line represents line of best fit. P-values given are for correlations.
Figure 6.
Observed correlation between dysregulated miRNAs and right hippocampal volume.
Graphs showing a significant correlation between miRNA expression levels and right hippocampal volume within the individuals with 22q11DS are shown. Open circles represent individuals with 22q11DS; the line represents line of best fit. P-values given are for each miRNA.
Figure 7.
Observed correlation between dysregulated miRNAs and whole brain volume.
Graphs showing a significant correlation between miRNA expression levels and whole brain volume within the individuals with 22q11DS are shown. Open circles represent individuals with 22q11DS; the line represents line of best fit. P-values given are for each miRNA.
Figure 8.
Proposed model of miRNA dysregulation in 22q11DS.
Decreased levels of free DGCR8 results in dysregulated expression of mature miRNAs, ultimately leading to development of the clinical phenotypes associated with 22q11DS.