Rare T-box variants in adult pulmonary arterial hypertension with congenital heart disease

We report the clinical and genetic features of three adult patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) carrying rare T-box variants. All three patients had weakness and cyanosis. Two patients had chest tightness, dry cough, and hemoptysis, and one patient had lower limb edema. Besides meeting the diagnostic criteria of CHD-PAH, three patients respectively presented the clinical features of specific syndromes. Specifically, patient 1 presented with clinical features consistent with tetralogy of Fallot, patient 2 presented with characteristics associated with small patella syndrome, and the patient 3 exhibited features consistent with Holt-Oram syndrome. Exome sequencing revealed that the TBX1 (c.820 T > C) variant was identified in patient 1, the TBX4 (c.251del) variant was detected in patient 2 and the TBX5 (c.486del) variant was found in patient 3. Our study for the first time found that CHD-PAH patients carry T-box gene variants, which has added new clues to understanding the pathogenesis of CHD-PAH and is expected to provide new targets and ideas for the diagnosis and treatment of CHD-PAH.