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Pulmonary Arterial Hypertension (PAH) is a severe complication of Connective Tissue Disease (CTD), with remarkable morbidity and mortality. However, the molecular and genetic basis of CTD-PAH remains incompletely understood. This study aimed to screen for genetic defects in a cohort of patients with CTD-PAH, using a PAH-specific panel of 35 genes. During recruitment, 79 patients were studied, including 59 Systemic Sclerosis patients (SSc) and 69 females. Disease-associated variants were observed in nine patients: 4 pathogenic/likely pathogenic variants in 4 different genes (<i>TBX4, ABCC8, KCNA5</i> and <i>GDF2/BMP9</i>) and 5 Variants of Unknown Significance (VUS) in 4 genes (<i>ABCC8, NOTCH3, TOPBP1</i> and <i>CTCFL</i>). One patient with mixed CTD had a frameshift pathogenic variant in <i>TBX4</i>. Two patients with SSc-PAH carried variants in <i>ABCC8</i>. A patient diagnosed with Systemic Lupus Erythematous (SLE) presented a pathogenic nonsense variant in <i>GDF2/BMP9</i>. Another patient with SSc-PAH presented a pathogenic variant in <i>KCNA5</i>. Four patients with SSc-PAH carried a VUS in <i>NOTCH1, CTCFL, CTCFL</i> and <i>TOPBP1</i>, respectively. These findings suggest that genetic factors may contribute to Pulmonary Vascular Disease (PVD) in CTD patients.