Mutational and clinical analysis of the ENG gene in patients with pulmonary arterial hypertension. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Pousada, Guillermo; Baloira, Adolfo; Fontán, Diego; Núñez, Marta; Valverde, Diana
• Is Part Of: BMC genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: Pulmonary arterial hypertension -- ENG gene -- Mutational analysis -- Functional study -- Genotype-phenotype correlation; Genetics -- Periodicals; 576.505
• DOI: 10.1186/s12863-016-0384-3
• Languages: English
• ISSNs: 1471-2156

Abstract

Abstract Background Pulmonary arterial hypertension (PAH) is a rare vascular disorder characterized by a capillary wedge pressure ≤ 15 mmHg and a mean pulmonary arterial pressure ≥ 25 mmHg at rest. PAH can be idiopathic, heritable or associated with other conditions. The aim of this study was to analyze the Endoglin (ENG ) gene and assess the influence of the c.572G > A (p.G191D) mutation in patients with idiopathic or associated PAH. The correlation between the pathogenic mutations and clinical and functional parameters was further analyzed. Results Sixteen different changes in theENG gene were found in 44 out of 57 patients. After in silico analysis, we classified eight mutations as pathogenic in 16 of patients. The c.572G>A (p.G191D) variation was observed in ten patients, and the analysis for the splicing process using hybrid minigenes, withpSPL3 vector to assess splicing alterations, do not generate a new transcript. Age at diagnosis (p = 0.049) and the 6-min walking test (p = 0.041) exhibited statistically significant differences between carriers and non-carriers of pathogenic mutations. Patients with pathogenic mutations exhibited disease symptoms 8 years before non-carriers. Five patients with pathogenic mutations were carriers of another mutation in theBMPR2 orACVRL1 genes. Conclusions We present a series of PAH patients with mutations in theENG gene, some of them not previously described, exhibiting clinical and hemodynamic alterations suggesting that the presence of these mutations may be associated with the severity of the disease. Moreover, genetic analysis in patients with PAH may be of clinical relevance and indicates the complexity of the genetic background. Graphical Abstract The role ofENG gene in patients with Pulmonary Arterial Hypertension.