title: Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations.
abstract: Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype.
authors.affiliation: Dept. Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, As Lagoas Marcosende S/N, 36310 Vigo, Spain.|Instituto de Investigación Sanitaria Galicia Sur, (IIS-Galicia Sur), Vigo, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Pousada
authors.affiliation: Complexo Hospitalario Universitario de Pontevedra, Servicio de Neumología, Pontevedra, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Baloira
authors.affiliation: Dept. Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, As Lagoas Marcosende S/N, 36310 Vigo, Spain.|Instituto de Investigación Sanitaria Galicia Sur, (IIS-Galicia Sur), Vigo, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Valverde
mesh_terms: D019295:Computational Biology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000503:physiopathology; D040582:Inheritance Patterns / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*