The Genetic Underpinnings of an Extremely Rare Disease
Jason Rose was diagnosed with Diamond-Blackfan anemia syndrome more than 50 years ago but only recently discovered the disease’s underlying cause.
As an infant, Jason Rose was diagnosed with Diamond-Blackfan anemia syndrome (DBAS), a rare disease affecting red blood cell production. This condition necessitated frequent blood transfusions and led to learning disabilities and short stature.
Still, Rose refused to let DBAS define him. He sought to identify the reason—the exact genetic mutation—responsible for the DBAS that was diagnosed more than 50 years ago .
“For 17 years I lived on packed red blood cell transfusions every two weeks and steroid therapy, until I went into spontaneous remission more than 34 years go,” Rose said. “You try to ignore the reality of how grave the disease can be if not cared for properly. I have dealt with my DBAS by not letting it define who I am and with the support of my loved ones and care professionals.”
One Genetic Change, Multiple Clinical Expressions
DBAS affects on average five to seven of the 4 million annual U.S. births and about 5,000 people worldwide. Common therapy regimens involve the aforementioned blood transfusions and, in Rose’s case, chelation therapy to prevent complications from iron overload. Stem cell transplantation is also a common consideration.
Determined to understand the genetic cause of his condition and remission, Rose sought answers from geneticists at UHealth – the University of Miami Health System. He has received care since September 2023 from Nicholas A. Borja, M.D., assistant professor of clinical and translational genetics at the University of Miami Miller School of Medicine, and was evaluated at the Miller School’s Undiagnosed Diseases Network site led by Mustafa Tekin, M.D., chair and professor in the Dr. John T. Macdonald Foundation Department of Human Genetics.
“Diamond-Blackfan anemia syndrome is a remarkable illustration of how a single genetic change can present with a variety of clinical features, including growth deficiency and anomalies in the bones, urogenital system and more,” Dr. Borja said. “The natural history of DBAS is also complex, as some patients remain transfusion-dependent, some respond to steroid therapy and a minority achieve complete remission.”
A Difficult Disease to Diagnose
While Rose received a DBAS diagnosis early, confirmation through molecular genetics took a long time. Genetic testing for DBAS wasn’t available when Rose was a kid. Physicians diagnosed the disease with bone marrow biopsy and blood tests until 2000.
I can’t emphasize enough how important it is for those with a rare disease to get genetically tested to find out what their condition is and how their health professionals can assist them in living a better quality of life.
Jason Rose
Over decades, Rose underwent tests to determine why he went into remission and to learn more about his disease. The search produced inconclusive findings in part due to the technological limitations of early gene sequencing.
“I lived with a disease for 17 years that was literally robbing me of life.” Rose said. “I endured hundreds of packed red blood cell transfusions to survive and then, one day, I began to spontaneously produce my own red blood cells. But why? How did it happen? I wanted to know more. I wanted an answer.”
Finding Answers to Genetic Mutations
Rose’s diagnostic journey took a positive turn when he turned to UHealth, where he’s worked since 2008, answering patient calls and scheduling appointments at UHealth Connect. His comfort with the health system and academic medicine was buttressed by the relatively recent identification of 10 to 20 gene mutations as DBAS causes.
“We came to suspect that Jason had something known as ‘revertant mosaicism,’ meaning that, as the cells in his blood continued to proliferate, they developed an additional mutation that essentially corrected the initial genetic change he was born with that caused Diamond-Blackfan,” Dr. Borja said. “With this hypothesis in mind, we chose to, instead of testing his blood cells, test the cells that line the inside of his cheek.”
Dr. Borja and team discovered a large deletion on chromosome 3 that included the RPL35A gene known to be responsible for up to 3% of DBAS cases. That finding was consistent with Rose’s clinical history and confirmed his initial diagnosis.
“My experience with being a survivor of DBAS is not to give up hope and never quit,” Rose said. “It was worth the wait to discover my genetic makeup, as the care I received with Dr. Borja was amazing. I can’t emphasize enough how important it is for those with a rare disease to get genetically tested to find out what their condition is and how their health professionals can assist them in living a better quality of life.”
Partners in Medical Discovery
Although there is no cure for DBAS, Rose continues to be in remission while he deals with complications. The trajectory for a DBAS patient is highly personalized. Each patient has a different experience.
“Patients are more than recipients of care. They are partners in pushing the field forward,” Dr. Borja said. “For providers, that’s the real gift of rare disease research—patients and clinicians learning and advancing together. Jason’s story exemplifies why we must remain open-minded. Even decades after a clinical diagnosis, it may take new technology or new clinical insights to discover the molecular underpinnings.”
Rose didn’t let his rare disease get the best of him. Told early on college wasn’t for him, he defied odds and graduated from Miami Dade College. He continued to Florida International University, where he graduated with a degree in political science. He remains a strong advocate for people with rare diseases, volunteers with veteran associations and enjoys photography.
“Having a rare disease no longer means you should be written off and hidden by society. You are a unique human being who has the willpower and ability to contribute,” Rose said. “Those with rare diseases should have an attitude of ability, not disability. We do not stop living or trying because it gets hard. We continue to persevere and we move forward, exceeding expectations.”
Tags: Dr. John T. Macdonald Foundation Department of Human Genetics, Dr. Mustafa Tekin, Dr. Nicholas Borja, genetics, rare diseases, Undiagnosed Diseases Network