Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report

BMC Pulmonary Medicine

Case Report

Guoliang Wang¹  Daniel J. Penny¹  Wenxin Zou¹  Yuxin Fan¹  Ruirui Ji¹  Rui Fan²  Nidhy P. Varghese³ 

[1] John Welsh Cardiovascular Diagnostic Laboratory, Section of Cardiology, Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, 1102 Bates Ave, Suite 430.09, 77030, Houston, TX, USA;John Welsh Cardiovascular Diagnostic Laboratory, Section of Cardiology, Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, 1102 Bates Ave, Suite 430.09, 77030, Houston, TX, USA;Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, 710032, Xi’an, Shanxi, China;Section of Pulmonology, Department of Pediatrics, Baylor College of Medicine, 77030, Houston, TX, USA;

关键词: Pulmonary arterial hypertension;    BMP9;    Nonsense mutation;   

DOI  :  10.1186/s12890-016-0183-7

 received in 2015-10-16, accepted in 2016-01-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPulmonary 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 presentationWe 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.ConclusionTo 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.

【 授权许可】

CC BY   
© Wang et al. 2016