[Hereditary pulmonary hypertension family with BMPR2 gene variation: a case report and literature review].

Objective: To describe the clinical characteristics, diagnosis, genetic features and treatment of hereditary pulmonary hypertension complicated with suspected hereditary hemorrhagic telangiectasia (HHT). Methods: Firstly, we summarized and analyzed the clinical data of two cases of suspected HHT admitted to the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University. Secondly, the genes of peripheral blood of patients and their families were completely sequenced and sanger sequencing was performed to verify the variation sites, and then the mRNA deletion caused by the variation was further verified. Thirdly, "HHT" "FPAH" and "BMPR2 gene variation" were used as keywords,and the related literatures of Wanfang database and PubMed database from January 2000 to November 2021 were searched and reviewed. Results: We found two patients in a family from Yiyang, Hunan province, who had symptoms of hemoptysis or pulmonary hypertension without epistaxis or other clinical features of HHT. However, both patients had pulmonary vascular abnormalities and pulmonary hypertension in their lungs. We found that BMPR2 gene variation (NM_001204.7:c.1128+1G>T) was positive and ENG, ACVRL1 and SMAD4 genes were negative. Family analysis and Sanger verification were carried out on 16 individuals in 4 generations of the family (7 of whom were found to carry the mutant gene), and then transcriptional level mRNA sequencing further confirmed that the variation resulted in the deletion of exon 8 and exon 9, and amino acid sequence estimation revealed that the amino acids of the protein from 323 to 425 were deleted. We thought that the incomplete translation of BMPR2 gene could lead to BMPRⅡ dysfunction. Therefore, it was diagnosed as hereditary pulmonary hypertension with suspected HHT. Both patients were suggested to reduce the pulmonary artery pressure, and at the same time, the whole-body imaging examination should be performed to screen other arteriovenous malformations, and the annual cardiac color Doppler ultrasound should be reviewed to evaluate the changes of pulmonary artery pressure. Conclusions: Hereditary pulmonary hypertension (HPAH) is a group of diseases with increasing pulmonary vascular resistance caused by genetic factors, including familial PAH and simple PAH. Variation in the BMPR2 gene is an important pathogenic factor of HPAH. Therefore, we should pay attention to the inquiry of family history when we clinically encounter young patients with pulmonary hypertension. If the cause is unknown, genetic testing is recommended. HHT is a rare autosomal dominant genetic disease. The possibility of this disease should be considered in clinical manifestations such as familial pulmonary vascular abnormality, pulmonary hypertension and recurrent epistaxis. There is no effective specific treatment for HPAH and HHT, which are treated symptomatically (including blood pressure reduction and hemostasis, etc.). It is suggested for these patients that pulmonary artery pressure should be dynamically monitored and have genetic counseling before giving birth.