For 15 years, Jonathan Jamoulis and his family searched for the cause of the medical condition that hounded them. At age 2, Jonathan had a congenital chest wall deformity surgically repaired. At age 19, Jonathan presented with chest pain and a cough. A CT scan revealed a large ascending aortic aneurysm. Jonathan is tall in stature with a high-arched palate and dental crowding; his care team suspected Marfan syndrome, but genetic testing came back negative. Left with few answers, he and his family turned to leading experts in the field of clinical genomics at Brigham and Women’s Hospital.
Using whole-genome sequencing, the Brigham Genomic Medicine (BGM) program helped to identify mutations in the LOX gene, a gene associated with the integrity of the arterial wall, that had never before been reported in patients.
"When we found this causal gene and were able to reveal it to the family, it was an emotional moment," said Natasha Frank, MD, a clinical geneticist at the Brigham. "Using genetic sequencing, we were able to answer the kind of question that hasn't been possible to address before and potentially change the lives of family members who can now be tested for mutations in this gene."
Brigham physicians are leveraging advancements in genomics to not only solve medical mysteries but also to help patients lead healthier lives and answer questions about future risk.
“There has never been a more exciting time or a more exciting place to be working in genomic medicine,” said Richard Maas, MD, PhD, chief of the Division of Genetics. “The ability of our talented, multidisciplinary faculty to work together as an integrated team is an extraordinary advantage when it comes to solving these challenging cases.”
At Brigham and Women’s Hospital, an integrated, multidisciplinary clinical and research team from BGM works together to help patients like Jonathan. Today, Jonathan is doing well and the gene mutations the Brigham investigators identified have been added to screening panels for Marfan syndrome and thoracic aortic aneurysm. BGM brings together world-class experts from across the Brigham and the entire Harvard-affiliated community to search for answers using the power of whole genome sequencing or whole exome sequencing, in combination with other genomic methods, and scour the genome for new genetic culprits.
The Brigham is part of the Undiagnosed Diseases Network (UDN), a research study funded by the National Institutes of Health (NIH) to help solve medical mysteries using genetic data. At the Brigham’s UDN site, BGM utilizes state-of-the-art genomic technologies and access to genomic information from healthy individuals to filter out non-disease-causing genes and mutations and focus in on genetic alterations that might be contributing to an individual’s disease. The results of this exhaustive search and comprehensive analysis can yield not only a diagnosis for a patient or family that has been desperately searching for one but may also offer information that could help guide novel treatment or predict if other family members are at risk.
“Our BGM experience has repeatedly demonstrated the power of multidisciplinary analysis of genomic sequencing data for patients whose rare, severe illnesses are not easily resolved through even the most advanced, clinically available testing,” said Joel Krier, MD, MMSc, clinical chief in the Division of Genetics at the Brigham and director of BGM.
Brigham experts are at the cutting edge of helping people understand how their genetic makeup impacts future disease risks, with the goal of tailoring medical care to keep people healthy for longer.
This summer, Brigham geneticists and genetic counselors launched the Preventive Genomics Clinic, the world’s first academic clinic where healthy adults and their children can learn about genetic predispositions before disease develops. Proactive testing options range from basic screening panels to comprehensive genome sequencing with analysis of thousands of disease-associated genes. Genetics clinicians then develop a customized plan (including referrals to specialists, screening/prevention options or medication recommendations) to help individuals access appropriate care based on their unique genetic information.
“Preventive genomics is not yet recommended as a standard of care,” said Robert C. Green, MD, MPH, a medical geneticist in the Division of Genetics and director of the new Preventive Genomics Clinic. “But for over two decades, our NIH-funded randomized trials in translational genomics have generated consistent evidence that there are more potential medical benefits and fewer risks than previously considered. It is time for this technology to be offered in a clinical context, under the care of genetics experts, to individuals who wish to be proactive about their health.”
The Brigham has also launched the Pharmacogenomics Clinic, which offers patients genetic testing that may help explain past medication responses as well as guide current and future medication therapy. A collaborative practice, the clinical team brings together a medical geneticist, a clinical pharmacist with specialized training in pharmacogenomics and a genetic counselor. Together, they can integrate genetic insights into improvements in patient care.
“It can take a long time to find the right medication or the right dose to help a patient feel healthy,” said genetic counselor Elizabeth Fieg, MS, CGC. “Pharmacogenomics represents a tool in the toolbox to help a provider make the best medication decision for their patient, improve care and improve trust.”
All of these ingredients, from unmatched faculty excellence to unwavering commitment to improved patient care, help comprise the “secret sauce” that makes the Brigham uniquely positioned to drive advancements in the new field of genomic medicine.
“The ability to provide a definitive molecular diagnosis to a patient or family with a vexing and previously undiagnosed condition, increasingly with positive implications for clinical care, is the best feeling a physician can experience,“ said Maas. “The Brigham has fully embraced this effort and is committed to being a world leader in the emerging field of genomic medicine.”
