Though we at Ingenuity and our customers spend most of our time knee-deep in scientific data, it is useful to take a look at the puzzles we are trying to solve from a completely different perspective.
That opportunity was offered to us at the 5th annual Consumer Genetics Conference in Boston, where opening keynote speaker (and Variant Analysis user) Hugh Rienhoff put a human face on the diagnostic odyssey that we so often think of in dry biomedical terms.
Rienhoff, a clinical geneticist by training and a biotech entrepreneur, detailed the story of his nine-year-old daughter Beatrice, who was born with an undescribed syndrome. Since her birth, Rienhoff has worked tirelessly to get a diagnosis for his daughter — and eventually to identify the genetic mutation underlying what may be a completely novel disease.
Rienhoff’s story was primarily that of a father desperately trying to help his daughter; his experience in clinical genetics served as an advantage that most parents don’t have, but it was not his focus. He chronicled innumerable efforts to track down the right experts in science and medicine, noting that he quickly learned not to tell people that the patient in question was his daughter; they were more likely to be interested if they didn’t think he was just another concerned parent. At one point, he had managed to narrow down the list of genes likely implicated in Beatrice’s syndrome, but he said nobody would sequence them for him because of IRB problems. He wound up sequencing the genes himself, getting instruments from places like eBay.
He also described the vast network of scientists and medical professionals who provided critical help on his quest, including Victor McKusick, who trained Rienhoff in clinical genetics; George Church; Malcolm Whitman; Gary Schroth; and many others.
Ultimately, Rienhoff’s tireless efforts and use of Variant Analysis led him to a mutation in TGF-β3 as the likely causative mutation. He and his network of volunteer experts are following up with functional studies, knocking the mutation into various systems (including frogs, human cell lines, and mice) to confirm that it leads to the symptoms his daughter has.
At the end of his talk, Rienhoff said, “We’re a post-genomic family.” He showed a picture of Beatrice with one of the model mice, joking that she is probably the only girl in the world who has a pet with her exact genotype. Throughout the talk, he gave a parent’s perspective, turning Beatrice from a proband into a person with a family. He told attendees that in order to succeed at this kind of diagnostic odyssey, “you have to be accustomed to failure” and that “pound for pound, patience and tenacity are worth more than cleverness.”
Rienhoff’s variant results were published in a paper entitled “A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with Marfan and Loeys–Dietz syndrome” in the American Journal of Medical Genetics this summer. The paper provides a live custom link to the data hosted by Ingenuity. You can view this supplementary data at: https://variants.ingenuity.com/Rienhoff2013.