Fig. 3

Study population and sequence data analysis. (a) Distribution of race/ethnicity among newborns sequenced in the three sample groups. (b) RUSPseq detected a relative larger number of DNA variants in methylmalonic acidemia (MMA) screen positives compared with gestational age (GA)/gender matched controls in all 72 genes, and (c) in the eight MMA-related genes, respectively. The sample size in each group is indicated at the bottom. (d) Pathogenic (P) and likely pathogenic (LP) variants in eight MMA genes were identified in each sample based on American College of Medical Genetics and Genomics (ACMG) standards and guidelines for interpretation of sequence variants.²⁸ For each group, the number of samples with P/LP variants is shown at the bottom. Two P/LP variants were detected in one or more MMA genes in 24 MMA patients, while 2 additional patients had only one P/LP variant, and 1 patient had one P/LP variant and a variant of unknown significance (VUS). No such variant combinations (e.g., two P/LP, or one P/LP and one VUS) were detected in healthy controls, while 2 MMA false positives had two variants in a MMA gene located in cis on the same chromosome.