Beaudet said that it will be important to identify the causative mutations for all individuals with serious Mendelian disorders. This information will allow for a better understanding of the type of variation found for each disease and the clinical utility of identifying various mutations.
De novo mutations that are not present prior to conception, such as trisomies, genetic deletions or duplications, and point mutations, can only be detected through intrapartum testing. Such testing, however, could also produce secondary findings that would pose a challenge to patients and providers. For example, Beaudet said, “we are doing now quite a large amount of prenatal diagnosis using copy number arrays where we encounter copy number variants of unclear significance.”
These secondary findings must be dealt with on a case-by-case basis, he said. He also stated that, in his opinion, more information is almost always better. He added, however, that “this is a personal opinion and not one I recommend for everybody.” But a physician giving a physical does not avoid listening to a patient’s heart because of the possibility of hearing a heart murmur. “We have the information that comes with the society and the technology that we currently live in,” he said.
The behavior of providers must be regulated through provisions such as the 2008 Genetic Information Nondiscrimination Act to prevent abuses. But most patients can be counseled through informed decision making, said Beaudet, even with findings of uncertain significance. Interpretation and annotation, though expensive today, could drop in price as informatics develop. Nevertheless, delivering information to patients will almost certainly involve considerable time and resources.
Beaudet concluded by pointing out that the pediatric community already has considerable interest in whole genome sequencing. The Baylor College of Medicine began offering whole genome sequencing in November 2011, and after several months it received between 10 and 20 samples per month. The most recent month saw 69 samples. Most were from children, but a few were from adults who were looking for an underlying genetic cause for a disease. In about 30 percent of the samples, testing is revealing a disease-causing mutation. The use of whole genome sequencing “seems to be on the rise,” he said.
The woman in the scenario may not know what to expect, said Michelle Gilats, a genetic counselor at the Chicago Center for Jewish Genetics. Though she is likely to have at least heard of Tay-Sachs disease, the patient is unlikely to know much, if anything, about the other conditions for which she is being tested. She is likely to expect that the testing will tell her whether her child will be at risk for certain conditions about which she