A similar pattern was also observed in two studies of American PAH families, where age of onset and penetrance was influenced by a second mutation, additional to BMPR2, in the TGFB1 gene in the first family and in the TGF-β regulating gene THBS1 in the second family [38, 39]. The gene discussed is TGFB1; the disease is pulmonary arterial hypertension.