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Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-β) signaling pathways. Defects in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722683/ https://www.ncbi.nlm.nih.gov/pubmed/26801773 http://dx.doi.org/10.1186/s12890-016-0183-7 |
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author | Wang, Guoliang Fan, Rui Ji, Ruirui Zou, Wenxin Penny, Daniel J. Varghese, Nidhy P. Fan, Yuxin |
author_facet | Wang, Guoliang Fan, Rui Ji, Ruirui Zou, Wenxin Penny, Daniel J. Varghese, Nidhy P. Fan, Yuxin |
author_sort | Wang, Guoliang |
collection | PubMed |
description | BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-β) signaling pathways. Defects in the BMP9 gene have been documented in hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, which is occasionally associated with PAH. Selective enhancement of endothelial BMPR2 with BMP9 reverses pulmonary arterial hypertension. CASE PRESENTATION: We report the case of a 5-year-old Hispanic boy who was diagnosed with severe PAH and right heart failure at 3 years of age. During his stay in the pediatric intensive care unit, treatment was initiated with inhaled nitric oxide and intravenous epoprostenol; he subsequently was transitioned to treprostinil, sildenafil, and prophylactic enoxaparin. Now, two years later, the child is asymptomatic on sildenafil, bosentan, subcutaneous treprostinil, and warfarin. Genetic screening revealed a novel homozygous nonsense mutation in the BMP9 gene (c.76C > T; p.Gln26Ter). The child had no telangiectasias or arteriovenous malformations; family history also was negative. Subsequent parental testing showed both parents were heterozygous for the same mutation, indicating that the child inherited the BMP9 mutant allele from each parent. CONCLUSION: To our knowledge, this is the first report of a BMP9 mutation in a patient with PAH. The homozygous nonsense mutation may account for the early onset and severity of PAH in this patient and also fit the ‘two-hit’ model we proposed previously. The absence of clinical symptoms for PAH in the parents may be due to incomplete penetrance or various expressivities of the BMP9 mutations. Our study expands the spectrum of phenotypes related to BMP9 mutations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-016-0183-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4722683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47226832016-01-23 Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report Wang, Guoliang Fan, Rui Ji, Ruirui Zou, Wenxin Penny, Daniel J. Varghese, Nidhy P. Fan, Yuxin BMC Pulm Med Case Report BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-β) signaling pathways. Defects in the BMP9 gene have been documented in hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, which is occasionally associated with PAH. Selective enhancement of endothelial BMPR2 with BMP9 reverses pulmonary arterial hypertension. CASE PRESENTATION: We report the case of a 5-year-old Hispanic boy who was diagnosed with severe PAH and right heart failure at 3 years of age. During his stay in the pediatric intensive care unit, treatment was initiated with inhaled nitric oxide and intravenous epoprostenol; he subsequently was transitioned to treprostinil, sildenafil, and prophylactic enoxaparin. Now, two years later, the child is asymptomatic on sildenafil, bosentan, subcutaneous treprostinil, and warfarin. Genetic screening revealed a novel homozygous nonsense mutation in the BMP9 gene (c.76C > T; p.Gln26Ter). The child had no telangiectasias or arteriovenous malformations; family history also was negative. Subsequent parental testing showed both parents were heterozygous for the same mutation, indicating that the child inherited the BMP9 mutant allele from each parent. CONCLUSION: To our knowledge, this is the first report of a BMP9 mutation in a patient with PAH. The homozygous nonsense mutation may account for the early onset and severity of PAH in this patient and also fit the ‘two-hit’ model we proposed previously. The absence of clinical symptoms for PAH in the parents may be due to incomplete penetrance or various expressivities of the BMP9 mutations. Our study expands the spectrum of phenotypes related to BMP9 mutations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-016-0183-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-22 /pmc/articles/PMC4722683/ /pubmed/26801773 http://dx.doi.org/10.1186/s12890-016-0183-7 Text en © Wang et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Case Report Wang, Guoliang Fan, Rui Ji, Ruirui Zou, Wenxin Penny, Daniel J. Varghese, Nidhy P. Fan, Yuxin Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report |
title | Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report |
title_full | Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report |
title_fullStr | Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report |
title_full_unstemmed | Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report |
title_short | Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report |
title_sort | novel homozygous bmp9 nonsense mutation causes pulmonary arterial hypertension: a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722683/ https://www.ncbi.nlm.nih.gov/pubmed/26801773 http://dx.doi.org/10.1186/s12890-016-0183-7 |
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