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. 2020 May 7;106(6):734–747. doi: 10.1016/j.ajhg.2020.04.006

Figure 2.

Figure 2

Serum Ca Concentrations for Individuals Having LoF or Rare Missense Variants in the DiscovEHR Cohort

(A) Box and whisker plot in the style of Tukey (points indicating outliers) of all serum Ca measures from the EHR summed for all individuals having the same nonsense or frameshift variant (# of individuals). White boxes indicate variants predicted to undergo NMD, gray boxes indicate variants predicted to escape NMD, and dotted lines mark the normal serum Ca concentration range from 8.5 to 10.2 mg/dL. Also plotted is the mean ± SD of all individuals (15,922) having no rare variants but homozygous for the reference (REF) haplotype (Ala986/Arg990/Glu1011, residue numbering corresponding to GenBank: NM_000388.4). ∗∗∗∗p < 0.0001.

(B) Upper plot presents the time series of serum Ca measures for an individual with a heterozygous Trp293∗ variant, showing a significant decrease in mean total serum Ca concentrations in December 2011, when treatment with cinacalcet began, as indicated by vertical dotted line (p < 0.0001). Means and 95% confidence intervals are plotted (mean prior to cinacalcet initiation, 11.23 ± 0.69 mg/dL, 95% C.I., 10.95–11.5 mg/dL; after cinacalcet initiation, 10.15 ± 0.69 mg/dL, 95% C.I., 9.81–10.48 mg/dL). Cinacalcet was continued through the beginning of 2015 and had a statistically significant effect on serum Ca concentrations (p < 0.0001). Lower plot indicates serum PTH values determined before and after cinacalcet initiation; differences in mean values were not significant.

(C) Serum Ca means (box and whiskers in style of Tukey with points indicating outliers) were plotted for individuals homozygous for the REF haplotype (15,922 individuals), and carriers of ClinVar and rare missense CASR variants that affect serum Ca concentrations (residue numbering according to GenBank: NM_000388.4). The number of carriers of each variant having serum Ca measures in the EHR are noted in parentheses. Dotted lines mark the normal range for serum calcium (8.5–10.2 mg/dL). Statistically significant differences between groups was determined by ANOVA (∗∗p < 0.01, ∗∗∗∗p < 0.0001).