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.