Fig. 2

Diagnostic yield of genome sequencing (GS) and phenotypic severity in multiple-hit patients. (a) Diagnostic yield of GS. Pie chart on left compares the proportion of patients with clinically relevant (CR) (pathogenic or likely pathogenic), potentially disorder-related (PDR) (e.g., candidate neurodevelopmental disorder [NDD] risk genes), and no risk variant identified. Middle pie chart compares the number of patients with multiple variants versus those with a single event. Right pie chart compares the number of such multiple events that can be resolved by exome sequencing (ES) or array comparative genomic hybridization (aCGH) (green) and those that cannot (yellow). (b) Comparison of full-scale IQ (FSIQ) for patients with multiple events (M), single events (S), and no event (N). Left panel considers both CR and PDR events (CR + PDR); right panel considers CR events only. (c) Burden analysis comparing the proportion of autism spectrum disorder (ASD) patients with and without intellectual disability (ID) for all CR + PDR or CR only events. (d) Overall burden analysis for patients with and without ID considering all CR + PDR or CR only events. P values were adjusted for multiple comparisons.