TheSOX17phenotype in pulmonary arterial hypertension: lessons for pathobiology and clinical management

Worldwide collaborative efforts to understand the genetic architecture of pulmonary arterial hypertension (PAH) have identified several gene variants and mutations in the past 5 years. With subsequent deep phenotyping, the clinical picture associated with these mutations is becoming more clear. For example, following the identification of pathogenic mutations in TBX4 and KDR [1, 2], histopathological and clinical phenotypes were described, with specific characteristics like small patella and bronchial diverticulosis for TBX4 and low diffusing capacity of the lung for carbon monoxide and interstitial changes for KDR [3–5]. Just as mutations identify key players in pathophysiology, the clinical and histopathological characterisation of mutation carriers provides insights into the cellular processes involved. SOX17 mutations in pulmonary arterial hypertension: phenotype and pathophysiological considerations