Next steps
Trio testing is powerful for the identification of de novo and
biallelic alterations confirmed in trans . In fact, 90.53% of our
GeneMatcher entries were for autosomal dominant de novooccurrences or autosomal recessive reports. Future identification of
elusive disease genes, such as those with lower penetrance or complex
inheritance patterns, will require extensive involvement in data-sharing
initiatives to further power disease gene discovery efforts. This will
be even more important as clinical DES use extends into varied clinical
settings. For example, expanding the clinical uses into the prenatal
clinic may ascertain more severe phenotypes not compatible with life and
therefore yet to be identified. As more commercially available panels
are run on an exome backbone, the ability to tailor gene content based
on the latest literature and proactively provide reclassification
results can extend to other testing platforms. Ongoing participation in
GeneMatcher and other Matchmaker Exchange platforms will heighten the
diagnostic and disease gene discovery power of DES.