Congenica, a global leader in the development of genome-based diagnostic technologies, has taken on a new project: to help a woman named Jill Viles with a serious muscle-wasting disease linked to a muscle-bound phenotype by offering to sequence her and her family’s genome.
Viles and her family are affected by Emery Dreifuss muscular dystrophy (EDMD), and hopes are that scientists can use their case to know more about this rare disease and improve future diagnoses and treatments for other patients.
“It will be fascinating to have this information, as we know of cases in which doctors have sequenced DNA from two members of the same family and found identical mutations – but one is healthy while the other shows symptoms. Understanding why this happens could help us find treatments for the condition,” Viles said in a press release.
During her university studies, Viles would spend nearly 25 hours a week researching her disease. In time she gathered pictures of EDMD patients and realized that all the symptoms reported were very much like those she and her family experienced.
Viles, 19, had already researched enough studies to suggest she and her family suffered from the condition, but doctors were still hesitant to issue a definitive diagnosis, so she took on the task herself to contact an Italian group of researchers who specialized in EDMD. She shipped blood samples from members of her family to Italy, but had to wait four years before she saw her diagnosis confirmed, in 1999.
The lead pathogenic mutation was eventually identified in the lamin A (LMNA) gene. Mutations in this gene can be highly repercussive with an extensive associated spectrum of conditions. Later on, while doing an internship at Johns Hopkins School of Medicine in Baltimore, Viles identified the condition as a specific form of the fat-wasting disease known as partial lipodystrophy, a specific subcategory known to block the body from storing fat in certain areas, such as the arms or legs.
Sometimes, mutations in LMNA cause patients to suffer from excessive growth of muscle tissue, which Viles saw in her father with his “Popeye” arms, and in her sister.
Viles was at a conference on lipodystrophy when she heard about a Canadian female Olympic athlete who had almost no fat but remarkably large muscles: Priscilla Lopes-Schliep. After doing more research, Viles found that Lopes-Schliep was missing fat in the same places as her family and was convinced that the athlete also had the LMNA mutation. Due to other genetic modifier mutations, Viles and Lopes-Schliep had radically different body types.
Viles and Lopes-Schliep ultimately got in touch with the help of David Epstein, an investigative reporter. Since then, the two women have become friends, and Lopes-Schliep underwent genetic testing at the University of Texas Southwestern Medical Center in Dallas.
Dr. Abhimanyu Garg, a renowned professional in lipodystrophy, was able to confirm Viles’ prediction: Both women suffered from different mutations in the same LMNA gene.
Viles also found that Lopes-Schliep was at serious risk from a dangerous level of triglycerides, and pushed her to get help as soon as possible. This was the second time that Viles’ persistence may have saved a life – the first was when she found her brother and father were at a higher risk of heart failure, which led her father to get a pacemaker; her brother is on a list to receive one later this year.
“We will use our expertise in the interpretation of genetic and genomic data and rare disease diagnosis to try to identify specific DNA sequences that ‘modify’ the way that LMNA mutations can cause drastically different clinical phenotypes. I think it’s a long shot that we’ll find anything, as it is a small number of genomes to analyze, but if we don’t look, we won’t know — we may get lucky,” said Phil Beales, M.D., Congenica’s co-founder and clinical director, and professor in the Department of Genetics and Genomic Medicine at University College London, England.
Congenica will cover the full cost of Viles and her family’s entire genome sequencing, analysis and interpretation, and will then provide Garg’s lab with its software to allow them to conduct their own analysis of the Viles family and other patients. Afterward, Viles will collaborate with Garg and Congenica on future steps.
Viles wants to help other people who suffer from EDMD and is now raising money with her own Jill Viles’ GoFundMe campaign to support additional research.
“These very rare mutations are spread out in patients all over the world, and it’s a really slow ordeal to have individual doctors studying them. I see a future where families can have a single blood test to diagnose their condition,” Viles said.
“If the information is readily available through a platform like Congenica’s Sapientia, the dozens of specialists and researchers will be better equipped to identify lipodystrophy or Emery-Dreifuss in their own labs. Then their patients won’t have to hunt through research papers and track down experts for answers,” she said.
Image Credits: Jill Viles’ GoFundMe campaign