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Molecular genetics of pulmonary arterial hypertension
Published on September 3, 2014 21 min
Other Talks in the Series: Molecular Genetics of Human Disease
Transcription factors and complex disease development
- Dr. Ines Pineda-Torra
- Division of Medicine University College London, UK
Gene therapy for the muscular dystrophies
- Prof. Jeff Chamberlain
- University of Washington, USA
Professor Richard Trembath and I'm going to talk to you today about the molecular genetics of pulmonary arterial hypertension.
Pulmonary hypertension is defined as an elevation of the pulmonary arterial pressure and has a multitude of causes. The recent classification from an expert group identified some of the associated conditions that can lead to an elevation of the pressure within the pulmonary arterial circulation. A noted important group of patients who have no known or recognized associated cause and fit into the category of heritable and idiopathic pulmonary arterial hypertension are the focus of this talk.
The characteristic histopathology of pulmonary arterial hypertension in its idiopathic and heritable form is one of increase in the smooth musculature of the pulmonary arterial circulation, a predisposition to formation of intravascular thrombosis and occlusion together with the pathognomonic plexiform lesions that are shown in this illustration in panel D.
Pulmonary arterial hypertension can and is frequently transmitted as a familial disorder. In this slide we show the characteristic pattern of inheritance with a autosomal dominant mode of transmission-- multiple affected family members over several generations. But clearly the gene is acting with reduced gene penetrance with individuals transmitting the disease indicated in the slide in gray, and yet not developing the characteristic clinical or histopathological features. Though it also indicated in the slide is the variable age of onset-- the numbers below the individuals indicating the age at which clinical symptoms became apparent. And finally, as is true for both idiopathic disease and when the disease is present within multiple family members, there is a sex bias despite the autosomal nature of the condition with females more frequently affected than males with the ratio of 2.5 to one.