Researchers from around the globe have joined together to study an unlikely subject in order to understand the genetics of HCM according to a paper published today in the journal eLIFE.
Dr. Christine Seidman, a cardiologist from Harvard Medical School, Dr. James Ware a geneticist from the MRC London Institute of Medical Sciences at Imperial College London, and Dr. Raúl Padrón, a structural biologist at the Venezuelan Institute for Scientific Research, have joined forces in order to study the tarantula.
The reason for their focus on the tarantula is because the proteins comprising the muscles inside the furry spider are actually very similar to proteins inside the human heart.
Dr. Seidman, who had taken note of Dr. Padrón’s work with spiders, sought him out at a meeting to discuss the similarity of heart proteins to those in tarantula muscles and asked him whether they might collaborate.
By studying the way that the spider proteins interact with one another, the scientists hope that they will gain further insight into whether and how certain genes cause different types of hereditary cardiomyopathy, including hypertrophic and dilated.
I hope that they find the answers soon, before any tarantulas escape from their lab!
A study published this week by HCM researchers in Canada found that double mutations in patients with hypertrophic cardiomyopathy are much less common than previously thought. In particular, researchers found that except for those with double mutations in the gene MYBPC3, there is not much data to support the finding that there is a worse clinical course for those patients who have double HCM mutations.
Hence, in the absence of extraordinary circumstances, such as two MYBPC3 mutations, the researchers caution that double mutations should not be the sole justification for the insertion of an implantable defibrillator.
The study looked at patients >18 years of age who underwent genetic testing at the Toronto General Hospital between January 2005 and June 2016. Out of a sample of 1411 patients, 9% of those who were gene-positive patients had 2 genes, but only in 1 case (0.4%) were both genes classified as those known to cause HCM.
In addition to looking at their own patients, the researchers also re-examined data from previously published studies. Similarly, they found when they re-analyzed the data that only 0.4% of the 8% of patients previously found to have double mutations in fact carried multiple pathogenic mutations.
When a patient is the only person in the family ever diagnosed with HCM, s/he will often wonder whether their disease is, in fact, genetic. S/he will also wonder whether it will be necessary for all first degree relatives to undergo serial screenings for the rest of their lives.
In answer to this concern, Australian researchers have recently identified a subset of HCM patients who appear to have a non-familial form of the disease and whose relatives may be candidates for less stringent screening protocols.
The study, just published in Circulation: Cardiovascular Genetics by Dr. Jodie Ingles and Dr. Chris Semsarian, found that this group, having neither genetic mutation associated with HCM nor family history of HCM, comprises approximately 40% of all HCM patients. Non-familial HCM patients are more likely to be older when diagnosed, and they often present with non-asymmetric hypertrophy and hypertension. And, these HCM patients appear to have a more favorable clinical course, with a better track record of survival from major cardiovascular events.
The researchers point out that by sorting patients into more distinct subgroups, doctors will be able to provide more personalized and evidence-based care to patients and their families. In particular, their recommendation is that first-degree relatives of non-familial HCM patients need only be screened one or more times in adulthood. Less frequent follow up surveillance is also suggested, in contrast with the more intensive screening guidelines recommended for family members of patients with familial HCM.
A study at the University of Amsterdam recently published in the Journal of Pediatrics found that most kids carrying a gene for HCM will not go on to develop HCM during their childhood.
The same study also found that gene positive children without overt signs of the disease are at relatively low risk for cardiac events.
The study included 119 children, positive for at least one HCM gene, with a median age of 12.1 years. 8 of these children (6.7%) received a HCM diagnosis within the time span of the study [which varied from 3.1 to 10.7 years]. 1 of the 8 diagnosed children suffered a cardiac event which necessitated implantation of an implantable cardioverter defibrillator or ICD.
The study did caution, however, that because severe hypertrophy and cardiac events may develop, it is important to refine risk stratification and long term follow up procedures for gene positive kids.
This informative blog article about genetic testing features practical advice about genetic testing and is taken from answers provided in a live presentation by Drs. John Jefferies and Ivan Wilmot.
Issues addressed include: how the test is administered, insurance issues related to the test and the meaning of a positive genetic test.
A study published today by Dr. Carolyn Ho, of Boston’s Brigham and Women’s Hospital, and colleagues, including Australia’s Christopher Semsarian, found that there are several factors which appear to stand out in young people who later go on to develop HCM.
The children/adolescents/young adults who participated in the study all carried at least one gene associated with HCM, and were members of families with strong histories of HCM. None of the 38 young people had clinical manifestations of HCM at the beginning of the study period, while 4 went on to develop HCM by the end of the study. In collecting the data analyzed in the study, the test results of the 4 individuals with HCM were compared to the 34 individuals that did not have HCM at the end of the study.
The factors associated with the development of overt HCM, as identified by the researchers, were: abnormal left ventricular relaxation and higher ejection fraction, EKG changes, longer mitral valve leaflets, higher NT-proBNP concentrations and troponin values.
In the conclusion, the authors acknowledged the need for further research and investigation in order to better understand the natural course and evolution of the disease.
A recent study published in The New England Journal of Medicine concluded that individuals of African descent found to carry genes previously identified with HCM did not, in fact, have the disease. Thus, the article highlighted the importance of including diverse populations when sequencing genomes for genetic diseases so as to avoid false diagnoses.
The New York Times also picked up this story, focusing its article on the negative repercussions that can result from a false positive genetic test for HCM.
In connection with the findings, National Public Radio interviewed three people, including Dr. Isaac Kohane, one of the researchers who published the findings of the lack of diversity in the HCM genetic panel, as well as New York City HCM patient Tarika Mingo. Finally, NPR spoke to veteran HCM expert Dr. Barry Maron, who noted a potential concern that athletes may have been erroneously disqualified from sports participation solely on the basis of false positive genetic testing results.
See also this story in the Wall Street Journal.
During the Olympics we all gather around our television sets to watch the best athletes in the world compete against each other and we wonder how it is that they can humanly perform at such a high level?
This feature story about Stanford HCM Clinic’s Dr. Euan Ashley provides us with an interesting overview of the research Dr. Ashley is doing on high performance elite athletes with the hope that their genes may provide clues that will one day help to help treat those of us with HCM and other genetic heart conditions.
MyoKardia, a San Francisco based bio-phamaceutical company developing drugs specifically for HCM and other genetic cardiomyopathies, announced data from their Stage 1 trials showing that the drug, MYK-461, benefits patients with HCM.
Specifically they found that the drug reduced ejection fractions and left ventricular outflow tract gradients in certain of the 101 individuals who participated in their Phase 1 trials.
The next step for the drug is to try to duplicate these findings in Phase 2 trials which will commence later this year.
A recent article in Science Daily discussed findings of geneticists in the Netherlands which revealed the existence of a mutation in the gene alpha-kinase 3 (ALPK3) which, if inherited from both parents, may cause severe cardiomyopathy in children.
Cardiomyopathy U.K. recently featured this story on their website.
See here for study.