2.2 Study design
The overall workflow is illustrated in Figure 1 . In total, 211 GDD/ID families were consecutively screened for eligibility from participating hospitals in China and105 patients met eligibility criteria. Parent-child trios/duos and affected family members (including siblings and grandparents) received GS when available. Five cases were later excluded due to the following reasons: (i) wrong samples (n=2), (ii) poor sequencing data (n=2), and (iii) variants were in the ES data but not detectable due to improper filtration (n=1). This resulted in analysis of GS data from 100 patients, parents, and affected family members. Data analysis was performed to find clinically relevant variants and candidate variant lists were sent back to the referring clinician to evaluate the possible diagnosis. At the end of the study, the undiagnosed GS patients were analyzed again with updated database and gene annotation. The definitive diagnosis information was collected to calculate the yield. The pathogenic variant(s) were compared to CMA/ES data to determine reasons for missed diagnoses.