Hugh Rienhoff’s quest to find a diagnosis for his daughter, Beatrice, (six, pictured) means many things to many people. He was seen as a trailblazer in personal genomics and do-it-yourself biology as he got to work on a second-hand PCR machine cloning genes from his daughter, who appears to have an undefined genetic disorder. While obviously of intense personal meaning, his project has increasingly spoken to the potential value of studying extremely rare human disorders. He broadened his quest with some help from friends and colleagues. He relies, he says on the “generosity of the interested.”
Now, he is collaborating with muscle researcher Alan Beggs of Boston Children’s Hospital, following up on a gene candidate that might be responsible for Bea’s condition. Her symptoms are varied, but seem to revolve around an inability to build much muscle (Although she needs leg braces, Rienhoff reported recently that she “is more of a firecracker every day.”)
We reported last September that Rienhoff had identified a gene that might be responsible for Bea’s condition. Illumina performed transcriptome sequencing on Bea, on Hugh and on his wife. With the help of researchers at a couple of different institutions they noticed that Bea had inherited variants of the CPNE-1 gene from both parents that appear to reduce dramatically its expression.
Rienhoff has since said that the few people to whom he’s presented his “Beatrice Hypothesis” have responded with “guarded enthusiasm.”
A blog post at Bio-IT World, today, indicates that the gene still appears to be promising, and Rienhoff is continuing to amass collaborators. Beggs is following up on it by looking at a big population of anonymous DNA sequence to get a sense of the prevalence of this variant. They’ve found individuals with two copies of the variant, but because of the anonymity of the data, it’s impossible to tell if they share any of Bea’s symptoms. “It’s kind of a pain in the ass to have that kind of information and not have medical history,” says Rienhoff. Beggs is also looking at some patients who do have similar symptoms to Bea’s and screening for the mutation. Rienhoff says he’ll think about buying a mouse with the gene knocked out if more support for the CPNE1 gene comes through.
Even if Rienhoff is approaching the end of his quest, he’s got a lot of other data to work through. Several individuals in search of diagnoses approached him through his website MydaughtersDNA.org and other routes and have had their transcriptomes sequenced by Illumina. Dealing with all that data is a lot of work, but gathering more data has become important in helping Rienhoff conscript help from others. It appears to be working. Beggs told Bio-IT world that Rienhoff’s case could benefit research tremendously: “The ability for a single individual to direct this kind of research into their own genetics is truly transformative for how we view genetic studies.”
Rienhoff is still blazing trails even while simply following his own. What’s surprising, however, is perhaps how as he progresses it looks less like a maverick DIY project and more like a traditional research program. “There’s no magic here just the usual slog.”
Photo C. Pickens