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