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BMC Medical Genetics

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Open Access 01-12-2017 | Research article

A systematic review of genetic mutations in pulmonary arterial hypertension

Authors: Gerardo Garcia-Rivas, Carlos Jerjes-Sánchez, David Rodriguez, José Garcia-Pelaez, Victor Trevino

Published in: BMC Medical Genetics | Issue 1/2017

Abstract

Background

Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9.

Methods

To provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests.

Results

Our results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH.

Conclusion

Our systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.

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Title: A systematic review of genetic mutations in pulmonary arterial hypertension
Authors: Gerardo Garcia-Rivas
Carlos Jerjes-Sánchez
David Rodriguez
José Garcia-Pelaez
Victor Trevino
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-017-0440-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

A systematic review of genetic mutations in pulmonary arterial hypertension

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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