A father’s quest to discover the reason, and hopefully a cure, for his daughter’s rare genetic disorder yields a never-before-seen gene mutation.
Of all the possibilities for “do-it-yourself” home projects—think go-carts, potato guns, and barbecue pits—chances are “sequencing DNA” isn’t on your list. But after going from doctor to doctor with his daughter Beatrice and getting little in the way of answers as to why she was unable to increase her muscle mass, Hugh Rienhoff Jr., MD, a biotech entrepreneur in California, took matters into his own hands. He bought equipment to sequence and study his daughter’s DNA at home, all by himself.
Rienhoff has become the poster boy for personal genetics, especially after a 2009 Wired piece about his daughter’s illness reached newsstands. Almost immediately after her birth in 2003, Rienhoff noticed something was wrong with his youngest child, Beatrice, or Bea for short. She appeared to have been born with some type of genetic disorder that caused her to be incredibly frail.
Unfortunately, though her symptoms seemed to suggest Marfan or Beals syndrome, doctors couldn’t find the culprit. And while physical therapy has helped, she remains weak. Now, the worry is that her disorder could affect her heart and lead to cardiovascular complications.
Nearly a decade after his quest began, Rienhoff still doesn’t have all the answers, but he has found the small mutation that is the likely cause of his daughter’s symptoms.
In 2009, Bea and the Rienhoff family became a test group for exome-sequencing technology at Illumina, a genome-sequencing company in San Diego, Calif. Exome-sequencing is different from genome sequencing in that it looks at the protein-encoding portion of a person’s DNA.
Bea’s exome includes an individual mutation in a gene that encodes a growth factor known as TGF-?3. Further experiments have shown that the faulty gene produces a non-functional protein, essentially disrupting the communication of and directions for a growth protein.
Bea’s gene mutation is changing the way her genes control cell growth, differentiation, and death. This entirely new mutation wouldn’t have been found if Rienhoff hadn’t taken his daughter’s health and well being into his own hands almost 10 years ago.
Even before Bea’s birth, Rienhoff was a player in the study of genetics. In a 2000 letter to the editor, he disagreed with the sentiment that genetic information won’t aid in making diagnoses, along with medical information provided in a family history. “Genetic information will be an improvement over the family history and, like the family history, will be used largely to set prior probabilities, not to make definitive diagnoses,” wrote Rienhoff in a letter to the New England Journal of Medicine (NEJM).
The claim that no interventions based on the identification of disease-related genes have yet proved safe and effective is premature, Rienhoff wrote. “This would be akin to saying, in 1900, that no interventions based on the identification of disease-related microbes have yet proved safe and effective,” he wrote to the NEJM. That would essentially be the same as saying that identifying viruses in order to create vaccines to fight them isn’t a good use of resources, something we now know is essential to the successful production of lifesaving vaccinations.
Let’s hope that a hundred years from now researchers look back at Rienhoff’s experiments as the start of a new approach to genetic study. While Bea’s condition isn’t yet defined, Rienhoff has a direction in which to look. The next steps include animal studies and, ideally, finding a living adult who displays Bea’s genetic mutation.