By Lillie Mermoud

Genetic testing can shed light on undiagnosed rare diseases that may not be found otherwise, offering medically actionable results that can help physicians inform and adapt a patient’s care plan. But what happens if you undergo genetic testing and don’t receive a diagnosis?

Even without a definitive diagnosis, the information gained from genetic testing can guide future testing, inform medical decisions, and offer peace of mind by ruling out certain conditions. This proactive approach can pave the way for better health management and potential breakthroughs in understanding rare diseases.

A life-changing diagnosis

Portia Pliam’s world changed on a normal day in second grade. During class, she started having a nosebleed. Her teacher sent her to the school nurse, and Portia thought nothing of it – she would be back in class soon. Thirty minutes later, the bleeding had not stopped. The school nurse called Portia’s parents, who took her to her pediatrician. Portia was diagnosed with essential thrombocythemia (ET), a rare type of blood cancer that causes bone marrow to make too many platelets. The body’s overproduction of platelets can lead to an increased risk of blood clots and stroke, bleeding problems, overall pain and discomfort, and extreme fatigue. Frequent monitoring by medical staff, as well as testing and prescription management, is necessary to keep a patient’s platelet count under control to prevent these serious, sometimes life-threatening, health problems.
When I was diagnosed, I was just a kid. All I wanted to know was if I could still play with my friends, go to school, and play squash,” said Portia. “But in the end, I’m grateful I was diagnosed so young because I was able to gradually adjust as I grew up. ET impacted my childhood, but as a kid, I felt so resilient and lived as if I didn’t have a life-threatening condition.

Understanding triple-negative essential thrombocythemia

Roughly 90 percent of ET cases are caused by differences in three genes linked to the disease: JAK2, MPL and 

CALR. Patients with ET usually undergo genetic testing to determine which gene is at play in their diagnosis, as this can provide critical information as to how the disease will progress, what treatments are most effective, and what health risks to screen for.

Ten percent of patients with ET don’t have any differences in JAK2, MPL and CALR genes, called triple-negative ET. Even though a gene hasn’t yet been identified for these patients, researchers and clinicians believe genetics are still at play, though further research is needed.

At the time of her diagnosis, Portia and her family were living in California and had access to Stanford Medical Center for genetic testing. After receiving whole genome sequencing, a comprehensive type of genetic testing, Portia found out she was one of the 10 percent who suffered from triple-negative ET.

While this offers her very few answers about the cause of her condition and little direction on how to treat it, this information has helped Portia rule out certain concerns associated with the JAK2, MPL and CALR genes. Most ET patients face a higher risk of developing leukemia than triple-negative ET patients do, offering Portia some peace of mind and allowing her care team to focus on managing her symptoms and improving her quality of life.

“When I first found out I was triple negative, I felt very alone,” said Portia. “It was as if no one else had experience with what I was going through.”

Whole genome sequencing at the Smith Family Clinic

Over time, her doctors placed her on medications to help lower her platelet count and manage her pain levels, but she hoped she might one day have a clearer diagnosis. When she was in high school, her father connected with Dr. Rick Myers, HudsonAlpha Institute for Biotechnology’s Chief Scientific Officer and President Emeritus. Dr. Myers suggested Portia travel to Huntsville, Alabama, where HudsonAlpha is located, to undergo genetic testing at the Smith Family Clinic for Genomic Medicine, a genetics diagnostic clinic on HudsonAlpha’s campus.

“I was adopted from China when I was one year old, so very little is known about my ancestry and family medical history,” said Portia. “The Smith Family Clinic’s reputation for quality whole genome sequencing and their expertise with rare disease made this seem like a good opportunity for me to learn more about who I am.”

Whole genome sequencing at the Smith Family Clinic confirmed Stanford’s diagnosis – Portia has triple-negative ET. However, she believes her time at the clinic was extremely valuable. Through HudsonAlpha’s own faculty members who research the genetics behind rare diseases, as well as the Institute’s collaborations with scientists around the world, the experience opened doors for further research.

“It wasn’t until I got a bit older and had testing at the Smith Family Clinic that I realized there is so much value in the genetic testing I did,” said Portia. “It gives me hope that my genomic data is in several databases for research around the country, and it means a lot to know that I can contribute to finding answers as more people are diagnosed.”

Knowledge gained from genetic testing is power

Today, Portia Pliam gives her all in everything she does. A rising senior at Wesleyan University, Portia keeps a busy schedule between her double majors in psychology and neuroscience and her role as captain of her university’s women’s squash team.

When she’s not leading her team to victory or studying for an upcoming exam, Portia serves as a patient advocate with MPN Advocacy and Education International. She gives talks about her experience as a patient and helps connect other ET patients with important resources.

“It feels good to know that I can help someone who is going through the same thing as me,” said Portia. “Most people are diagnosed with ET later in life. Pediatric ET and young adults with ET are rare, and because of that, those patients don’t have much information about what symptoms to look for, what to do to improve their quality of life, or how the disease progresses. Sharing my story is an opportunity to help someone access information they might not have had before.”

In between her studies and advocacy work, Portia is making important strides toward advancing her future career. She dreams of going to medical school and working in oncology to impact others the way her physicians have helped her.

Her unique experience as a patient and as a pre-med student has given her an interest in genetics and genomics, which she hopes to carry with her into her future career. Over the summer of 2024, Portia took on a prestigious internship at HudsonAlpha  as a BioTrain intern, working in the Myers lab and focusing on the genomics of neurodegenerative diseases.

“Coming back to HudsonAlpha as an intern after being a patient at the Smith Family Clinic felt like a full circle moment,” said Portia. “I understand firsthand the value of the work that is being done there. I’m grateful to have been able to grow my lab skills at HudsonAlpha because that will help me launch my career and help people down the line. And I’m grateful for my experience at the Smith Family Clinic. I believe genetic knowledge is power, no matter if your test was conclusive or not.”