Patients who undergo broad DNA testing to explain a specific medical condition also should be told about chance findings that indicate risk for other serious diseases, a group of genetic specialists said.
Laboratories that conduct complete gene sequencing on patients should analyze and report on about 60 genes with known links to potentially grave conditions, such as hereditary cancers and heart conditions that can be prevented and treated, according to a report released today by a working group of the American College of Medical Genetics.
As the price of DNA analysis drops, doctors more often turn to analyzing the genome, an individual’s complete genetic code, for mutations that might explain a patient’s illness. These wider searches increase the likelihood of discovering unexpected disease-linked genes, often called “incidental findings,” said Robert Green, a Harvard Medical School geneticist and chairman of the panel.
“The disruptive technology of sequencing is calling for us to respond,” said Green, who is also a researcher at Brigham and Women’s Hospital in Boston. “These are all gene variants that could make an enormous difference in a patient’s future medical health.”
The guidelines apply to children and adults, the report said.
Faster, cheaper DNA analyzers made by Life Technologies Corp. and Illumina Inc. have dropped the price of sequencing a single human genome to about $4,000 from more than $2 billion in 2001. Government projects in the U.S., U.K., and the Faroe Islands in the North Atlantic are planning to sequence the genomes of millions of people for research and treatment.
Mutations listed in the guidelines include those that raise the risk of breast and colon cancer, heart conditions such as hypertrophic cardiomyopathy and blood disorders such as familial hypercholesterolemia. These mutations should be reported to doctors, who can decide when and how to discuss the information with patients and families, the panel said.
“In most of these cases, if these mutations appear in a patient’s report, it’s going to be pretty difficult for the doctor to avoid discussing it,” Green said.
Many of the diseases on the list, such as inherited cancers, are likely to arise later in life. The guidelines recommend that when mutations tied to those diseases occur in children, they should be put in the patient’s file and shared with parents, just like any other sign of disease risk.
“An incidental finding relevant to adult disease that is discovered and reported through clinical sequencing of a child may be the only way in which that variant will come to light for the parent,” the panel’s report said.
Children with rare or previously unseen medical conditions are often candidates for genome sequencing, because their conditions may be caused by unique or unfamiliar mutations. Sifting through these patients’ genomes for genes that may raise the risk of disease decades later is unnecessary and unfair to children, who have no way to determine their own preferences at the time, said Stephen Kingsmore, a pediatric geneticist at Children’s Mercy Hospital in Kansas City, Missouri.
Kingsmore has established a service for children with rare diseases that can sequence and analyze their genomes in about a week, far faster than ever before. He says he deliberately leaves unanalyzed any portions of their genomes that may relate to adult conditions.
“The parents want to know something that’s relevant to acute illness in the child,” he said in a telephone interview. “The risk that the child may have elevated cholesterol at age 30 is irrelevant.”
Mutations linked to genetic diseases that can’t be treated or prevented, such as Huntington’s disease, a progressive neurological disorder, aren’t on the list. Neither are many genetic mutations that are only loosely connected to diseases.
The recommendations, especially those relating to children, are likely to remain controversial, Green said. The working group recommended that the guidelines undergo review at least annually as the health impact of the mutations, the use of the guidelines, and patients’ reactions become better understood, he said.
“If the implementation of these recommendations demonstrated results in discomfort or harm, I’d be the first one to suggest changing them,” he said.