The Missing LINC for Genetic Cardiovascular Disease?
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
- atrial fibrillation
- cardiovascular diseases
- heart failure
- nuclear envelope
- nuclear pore
As of 2014, cardiovascular disease (CVD) was listed as the underlying cause for 1 of every 3 deaths in the United States.1 Many forms of CVD have a strong genetic component, and the number of causal genes elucidated greatly depends on the type of CVD under study. Understanding the molecular basis of CVD can guide medical decisions of the practitioner, patient, and family members. Currently, gene panels are used in the clinical setting to screen for disease-causing variation. Panels vary greatly in size depending on the number of genetic causes of the disease in question. There is often a great deal of phenotypic overlap between the inherited CVDs. To accommodate these variable phenotypes, many testing laboratories now use large panels that include >75 genes. Another route that is more commonly being used is the use of whole exome sequencing and whole genome sequencing to identify causal and contributory variants.2,3 Whole exome sequencing or whole genome sequencing can begin with focus on rare variants in genes most commonly associated with disease, and, if no attractive candidates are identified, the search is broadened to include genes not currently associated with disease. Such broad searches can lead to the identification of new disease genes; a great benefit in the research context, but a burden in the clinical-setting making disease risk assessment more difficult. It is also an ever-evolving target to determine the amount of validation necessary to deem variants pathogenic and therefore reportable, especially when variants are unique to individuals or to individual families.4 It can be especially troubling when the disease in question involves sudden death where there is significant risk for surviving family members. It is imperative that new, potential CVD genes continue to be validated using a variety of methods, including family studies, animal- and …