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Pulmonary Vascular Disease |

Mutational Analysis of BMPR2, KCNA5, and ACVRL Genes in Patients With Pulmonary Arterial Hypertension

Guillermo Pousada, PhD; Adolfo Villar, MD; Carlos Vilariño, MD; Diana Valverde, PhD
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University of Vigo, Vigo, Spain


Chest. 2014;145(3_MeetingAbstracts):511A. doi:10.1378/chest.1836245
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Abstract

SESSION TITLE: Pulmonary Hypertension Posters II

SESSION TYPE: Poster Presentations

PRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PM

PURPOSE: Pulmonary arterial hypertension (PAH; OMIM 178600) is a rare disorder characterized by obstruction of precapillary pulmonary arteries. PAH results from extensive remodelling of the pulmonary vasculature caused by an increased musculation and the fibrosis of the intima that leads to obliteration of small pulmonary arteries. The 75% of patients with familial form of PAH have a mutation in the gene encoding bone morphogenetic protein receptor type II (BMPR2). However, some other candidate genes have been advocated, including the KCNA5 gene that codifies for a potassium voltage-gated channel and ACVRL (Activin A receptor type II-like 1). These genes are located on chromosomes 12p13 and 12q13 respectively.

METHODS: Forty one patients with PAH and 50 controls were included in this study. The BMPR2, KCNA5 y ACVRL genes were amplified by PCR and sequenced.

RESULTS: A total of 31 variations were identified in 33 of patients in BMPR2 gene. Only 8 changes were identify as pathogenic in 9 patients (C84F, Q92L, Q109H, A162P, Y218X, D264N, W298X, V341M). For KCNA5 gene 12 changes were detected in 18 patients. Three were classified as pathogenic in 4 patients (P169R, R184P, E208X). In ACVRL gene 12 variations were detected in 30 patients and 1 was classified as pathogenic in 1 patient (S225C). The pathogenic mutations were found in 34% of patients and none were detected in a panel of 100 chromosomes from control individuals. The mutations that produce effects in splicing are present in 54% of patients.

CONCLUSIONS: In conclusion, the changes found in these genes indicated that are the most important genes implicated in the development of PAH and these mutations may predispose individuals to an increased risk of developing of PAH.

CLINICAL IMPLICATIONS: The main clinical implication of this study is to determine the presence of pathogenic mutations and so early diagnostic relatives. Another goal is to make a genotype-phenotype assessment.

DISCLOSURE: The following authors have nothing to disclose: Guillermo Pousada, Adolfo Villar, Carlos Vilariño, Diana Valverde

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