Whole-exome sequencing identified a novel mutation of BMPR2 in a Chinese family with pulmonary arterial hypertension

Abstract

BMPR2 encodes the bone morphogenetic protein receptor type 2. Most of heritable pulmonary arterial hypertension is caused by mutations of BMPR2. Pulmonary arterial hypertension is characterized by increased pulmonary vascular resistance and sustained elevation of mean pulmonary arterial pressure. Here we sought to identify novel mutations in a family with pulmonary arterial hypertension. Whole-exome sequencing obtained variants data from the patient's blood Genomic DNA who was diagnosed with pulmonary arterial hypertension. Sanger sequencing was used to confirm potential causative variants in the patient. A novel frame-shift mutation in BMPR2 (NM_001204:c.453dupA, p.I152Nfs*29) was identified in the patient with pulmonary arterial hypertension, she also had subclinical hypothyroidism and hyperuricemia. This frame-shift mutation will cause the BMPR2 protein loss of function, leading to the obstruction of BMPs signaling pathway, further affect the growth, proliferation and differentiation of vascular cells. Our study expands the spectrum of BMPR2 mutations and enriches the clinical features.

KEYWORDS:

• BMPR2
• pulmonary arterial hypertension
• subclinical hypothyroidism
• hyperuricemia
• whole-exome sequencing

Acknowledgements

The authors thank all subjects for participating in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Consent for publication

Written informed consent for publication of their details was obtained from the patient.

Data availability statement

Due to patient privacy, additional supporting data, including genetic data is not available.

Additional information

Funding

This study was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China [grant number 2017ZX10103005-006], the National Natural Science Foundation of China [grant number 81970403], the Fundamental Research Funds for the Central Universities of Hunan Province [grant number CX20190104], the Natural Science Foundation of Hunan province [grant number 2018JJ2645] and the Fundamental Research Funds for Central Universities of Central South University [grant number 2019zzts461].