Curing Rare Diseases — 12

Asimilar approach has been used in adults who are in the intensive care unit with an unknown diagnosis, using sequencing to crack the case within five to seven hours. My team at Scripps Research and those at several other academic centers have offered whole genome sequencing as a way to unravel the diagnosis when the patient has a serious and chronic unknown condition. We’ve applied that research program for hundreds of individuals and have had a success rate of about 40 to 50 percent for getting to the root molecular cause, often identifying a treatment that can help the patient’s condition. Another important application of sequencing is known as “molecular autopsy.” The concept is that a sudden unexpected death in a person younger than forty to fifty years old warrants whole genome sequencing of the deceased for a molecular diagnosis. If a gene mutation is identified that has been implicated with sudden death, children can also undergo sequencing. This approach can be both lifesaving for descendants of the deceased and reassuring for offspring to know they do not harbor the genomic susceptibility.

The genomic “fast lane” for determining cancer diagnosis during surgery is an exciting initiative that is starting to get traction. For example, in Melbourne, Australia, in 2024, just forty minutes after a biopsy was obtained using a portable sequencing device, forty-five of fifty tumor samples were accurately classified for cancer type. Whether to proceed with aggressive surgery or not was clear. In the years ahead, whole genome sequencing will become more routine for assessing risk.

Genomics England is conducting a research project of sequencing two hundred thousand babies, not just to find rare genetic diseases but also to predict risks of adult conditions and define drug sensitivities. Similar programs of newborn sequencing have been launched in the United States (one hundred thousand newborns), Belgium (forty thousand newborns), Greece, Australia, France, and the European Union. Tens of thousands of healthy newborns are being sequenced for four hundred genetic diseases that have treatment options through a consortium coordinated at Rady Children’s Institute for Genomic Medicine, a research partner of ours. The combined features of low-cost, rapid, and accurate data interpretation with AI as well as emerging evidence for improving patient outcomes all point to increasing use of reading genomes for medical diagnosis and care.