Spectrum and distribution of deleterious germ line variants among subgroups and association with age at diagnosis. (A) Bar chart depicting the number of confirmed P/LP germ line variants per gene identified in 28 patients with MDS. Compound heterozygous variants in the AR gene SBDS were counted as 1 variant per patient. Color schematic: purple, DDX41; green, general tumor predisposition genes; blue, telomere biology disorders; red, bone marrow failure genes; gray, others. (B) Nested pie chart showing the distribution of gene subgroups as well as biological functions. (C) Violin plots of the age at diagnosis of the 4 most common groups of predisposition syndromes identified in this study. (D) Association between the affected gene in the germ line and the age at MDS diagnosis. The data are derived from our study (confirmed/presumed germ line, n = 44) and other larger cross-sectional studies on germ line variants in patients with MDS using either panel-based or WES covering most genes of interest.^5-8,12,15,57 Each circle represents a gene, and the circle size corresponds to the frequency of variants within this gene in the total cohort. Genes in the upper left quadrant were associated with an age at diagnosis of less than 40 years, whereas genes in the upper right quadrant were associated with an age at diagnosis greater than 40 years, based on calculated odds ratio. Color schematic: purple, DDX41; green, general tumor predisposition genes; blue, telomere biology disorders; red, bone marrow failure genes; gray, others. DSB, double-strand break repair; MMR, mismatch repair; RM, ribosome maturation.