PAH Genetic Risk Factors Collected in New, Comprehensive Database Could Improve Diagnosis, Treatment Decisions

PAH Genetic Risk Factors Collected in New, Comprehensive Database Could Improve Diagnosis, Treatment Decisions

Known genetic risk factors associated with PAH (Pulmonary Arterial Hypertension) have been organized and assembled by researchers in an updated compilation, freely available on the public repository ClinVar.

This important new study, led by Dr. Rajiv Machado from the University of Lincoln School of Life Sciences, UK and published in the online academic journal Human Mutation, constitutes the most complete collection of defective variations in the 10 characterized genes associated with the disease. The information gathered by the scientists studying PAH was obtained from hundreds of patient records from specialist PAH centers located in Germany, France, the UK and North America.

Genetic defects are one of the causes of pulmonary arterial hypertension. The disease is characterized by abnormal constriction of the pulmonary artery, forcing the heart to work harder and leading to high blood pressure in the lungs. PAH is a life-threatening condition due to the increasing blood pressure over time that can eventually result in heart failure.

Genetic data observed to date identifies mutations in the BMPR2 gene as the leading cause for patients with a family history of the disease. Defective variations capable of causing the disease have, however, been identified in approximately 25% of patients in non-hereditary cases. This new compilation comprises 370 independent mutations of BMPR2 not included or newly discovered (81 of the additions) since the 2009 update by Dr. Machado’s research team. Next-generation sequencing (NGS) allowed researchers to identify and sequence the rare, novel mutations in PAH patients’ genetic profiles quickly and inexpensively.


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The relevance of this new study is highlighted by Dr. Machado, “This is the most comprehensive and complete compilation of all defective variations in the genetic risk factors for PAH. This will allow the clinical geneticists, with a greater degree of certainty, to conclude that the gene variations present in a patient are either disease causing or of unknown significance.” Patient-related advantages of databases such as these include an easier and more accurate clinical diagnosis, new information for genetic counseling and patients’ decisions regarding family life, and a more personalized patient management and care. The identification of genetic variations also provides insights in the molecular mechanisms of the disease and new potential drug targets for PAH therapy.

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