ABCA3 Gene Mutations in Late Preterm and Term Infants With Fatal Unexplained Respiratory Distress Syndrome

Respiratory distress syndrome (RDS) is the most common respiratory cause of mortality and morbidity in very preterm infants, but it also could be seen in late preterm and term infants. Some genetic mechanisms were involved in the pathogenesis of RDS in late preterm and term infants.

ATP-binding cassette transporter A3 (ABCA3) is essential for the production of pulmonary surfactant, whose mutation is the most common monogenetic cause of RDS in newborns. It also takes a vital role on unexplained RDS (URDS) in late preterm and term infants. Some previous studies showed that URDS with homozygous or compound heterozygous ABCA3 mutations had high mortality, while different mutation types could lead to different outcomes. However, most of the study focused on URDS with ABCA3 gene mutations, and there is no evidence that URDS without confirmed gene mutations have relatively better or worse outcomes. Furthermore, all the population in previous study are non-Asian races, which indicated that all the study conclusion is not applicable in Asia.

Based on the next-generation sequencing technology, exome sequencing has been widely used in the clinic. In our neonatal intensive care unit (NICU), a clinic exome sequencing was usually performed in infants with fatal URDS. The present study was designed to compare the URDS with ABCA3 gene mutations with those without confirmed gene mutations and to establish the relationship between various ABCA3 gene mutations and variant RDS severity and outcomes.