Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic...

Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH.

Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3months of age; moderate of severe PH at 1month of age with death occurring prior to the 3month echocardiogram; or on PH medications at 1month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations.

There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes.

Prognosis study LEVEL OF EVIDENCE: Level IV.