Open Access
ARTICLE
Whole Exome Sequencing Identifies A Novel Pathogenic Bmpr2 Variant in Pulmonary Atresia
Muyu Qi1,#, Xiaoping Lan2,#, Jia Li1, Junwen Ge1, Li Shen1,*, Rufang Zhang1,*
1
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai, China
2
Molecular Diagnostic Laboratory, Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai, China
* Corresponding Authors: Li Shen. Email: ; Rufang Zhang. Email:
# The authors contribute equally
Congenital Heart Disease 2021, 16(5), 487-498. https://doi.org/10.32604/CHD.2021.015887
Received 25 January 2021; Accepted 01 April 2021; Issue published 03 June 2021
Abstract
Objective: Pulmonary atresia (PA) is a rare type of complex cyanotic congenital heart defect characterized primarily by an undeveloped pulmonary valve or pulmonary artery. Therefore, defining a disease-causing gene
mutation in a pulmonary atresia family is a possible method of genetic counseling, future prenatal diagnosis,
and therapeutic approaches for pulmonary atresia.
Methods: Blood samples were collected from six PA family
members, and genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. Gene detection was performed using a second-generation sequencing gene panel.
Results: Genetic testing results indicated that a heterozygous mutation originating from maternal inheritance was detected in the
BMPR2 gene of the proband’s
genomic DNA. The pathogenic gene was c.2804C>T (p. A935V). The mutation was also detected in the genomic
DNA of the proband’s elder brother (III-1), but not in other family members.
Conclusion: To the best of our
knowledge, this is the first study to report the BMPR2 variant responsible for pulmonary atresia. The frequency
of the c.2804C>T (p. A935V) mutation detected in this family is extremely low in the normal population (1/
246048). The mutation was highly conserved among different species. Sorting intolerant from tolerant (SIFT) predicts it to be a harmful mutation.
Keywords
Cite This Article
Qi, M., Lan, X., Li, J., Ge, J., Shen, L. et al. (2021). Whole Exome Sequencing Identifies A Novel Pathogenic
Bmpr2 Variant in Pulmonary Atresia.
Congenital Heart Disease, 16(5), 487–498.