Following Biology's Lead
Every year, 50,000 infants are born in the United States with a constellation of symptoms that boils down to a genetic glitch. For many, doctors can offer a diagnosis: Tay-Sachs, a neural tube defect, a metabolic disorder. Even if the news is not good, health care professionals have enough insight to help families prepare for what’s to come.
Some conditions, though, are so rare and so poorly understood that doctors have little to offer by way of diagnosis or consolation, and families spend years on a painful and expensive quest for answers. Increasingly, however, clinician-scientists at academic medical centers are offering whole exome sequencing (WES), a technique for analyzing all of a patient’s protein-encoding genes using a few vials of blood. Developed for research applications, the technique is now frequently covered by insurance and available as a diagnostic tool.
A Columbia team in 2014 reported on the results of WES for 115 patients. “Our experience should assist other clinicians in implementing WES into their clinical practice because we have addressed practical concerns including patient education in pretest counseling, consent, insurance coverage, turnaround time, yield of testing, updates of test results, and impact on clinical care,” the researchers wrote. “We have found that WES significantly improves our diagnostic ability; we have addressed many of the practical problems of its clinical implementation and routinely use WES as a primary test in patients’ genetic evaluation.”
The individuals who received WES all had an undefined genetic disorder and were patients of Wendy Chung, MD, PhD, who directs the clinical genetics program at Columbia University Medical Center, and two members of the Division of Clinical Genetics in the Department of Pediatrics, Kwame Anyane-Yeboa, MD, and Alejandro Iglesias, MD. WES yielded a definitive genetic diagnosis for 32 percent of the patients, and in many cases helped inform families about better treatment options.
WES is particularly valuable for the youngest patients, the team noted, because diagnostically relevant symptoms and signs may take time to emerge, delaying effective treatment. “A diagnosis made early can be particularly valuable to identify additional associated features of clinical syndromes before they become symptomatic to prevent or ameliorate the manifestations and to minimize the diagnostic evaluation of new symptoms.” Such was the case for three of the patients in the study.
Diagnoses based on WES allowed all of the patients to avoid more invasive diagnostic procedures, such as muscle biopsy. Results also helped several families alter medical management, access social and educational services available only to individuals with a clear diagnosis, identify other family members at risk for the condition, and make informed decisions about reproductive planning.
“When we’ve exhausted the routine clinical diagnostics, we go beyond clinical care and use novel research methods,” says Dr. Chung. “Genomic sequencing, with the purpose of being comprehensive, answers a very relevant clinical question using the most advanced genomic tools to get at the answer. We go into it without preconceived notions and just go where the biology takes us.”
This is a summary of research published in Genetics in Medicine, December 2014.