Whole Exome Sequencing Identifies a Novel Pathogenic BMPR2 Variant in Pulmonary Atresia

Objective: Pulmonary atresia (PA) is a rare type of complex cyanotic congenital heart defect mainly characterized by an undeveloped pulmonary valve or pulmonary artery. herefore, defining a disease-causing gene mutation in a pulmonary atresia family becomes a possible method of the genetic counseling, future prenatal diagnosis, and therapeutic approaches of pulmonary atresia. Methods Blood samples of six members in a PA family were collected, and the genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. The gene detection was performed using the second-generation sequencing gene Panel. Results Genetic testing results indicates as follows: A heterozygous mutation originated from maternal inheritance was detected in the BMPR2 gene of the proband’s genomic DNA. The pathogenic gene was at 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 our knowledge, this is the first study to report the BMPR2 variant responsible for pulmonary atresia. The frequency of c.2804C>T (p. A935V) mutation detected in this family is extremely low in the normal population (1/ 246048). The mutation was highly conservative in different species. And SIFT (sorting intorlerant from tolerant) predicts it to be a harmful mutation.