If this search for rearrangements is unproductive, a systematic study of the genes involved may be undertaken to search for mutations (this technique is called clinical exome sequencing). The number of genes analysed varies according to the examination but typically involves between 100 and 5,000 genes. Diagnostic yield depends on the underlying problem and may be as high as 50%. A recent analysis has documented the positive, useful outcomes of this approach for patient management and for the reproductive decisions of families (Genet Med 2020; 22:986-1004).

Two strategies are explored:

one involves the joint analysis of both parents (trio analysis) and speeds up the discovery of mutations occurring for the first time in the child whilst not present in the parents (de novo mutations).
In the other, the parents are also analysed but only in a targeted way, to establish how the previously identified mutation is inherited (either present in one or both parents, or absent in the parents).

Genesupport - Children developmental anomalies