Surfactant proteins gene variants in premature newborn infants with severe respiratory distress syndrome

J Perinatol. 2018 Apr;38(4):337-344. doi: 10.1038/s41372-017-0018-2. Epub 2017 Dec 19.

Abstract

Objective: Genetic surfactant dysfunction causes respiratory failure in term and near-term newborn infants, but little is known of such condition in prematures. We evaluated genetic surfactant dysfunction in premature newborn infants with severe RDS.

Patients and methods: A total of 68 preterm newborn infants with gestational age ≤32 weeks affected by unusually severe RDS were analysed for mutations in SFTPB, SFTPC and ABCA3. Therapies included oxygen supplementation, nasal CPAP, different modalities of ventilatory support, administration of exogenous surfactant, inhaled nitric oxide and steroids. Molecular analyses were performed on genomic DNA extracted from peripheral blood and Sanger sequencing of whole gene coding regions and intron junctions. In one case histology and electron microscopy on lung tissue was performed.

Results: Heterozygous previously described rare or novel variants in surfactant proteins genes ABCA3, SFTPB and SFTPC were identified in 24 newborn infants. In total, 11 infants died at age of 2 to 6 months. Ultrastructural analysis of lung tissue of one infant showed features suggesting ABCA3 dysfunction.

Discussion: Rare or novel genetic variants in genes encoding surfactant proteins were identified in a large proportion (35%) of premature newborn infants with particularly severe RDS. We speculate that interaction of developmental immaturity of surfactant production in association with abnormalities of surfactant metabolism of genetic origin may have a synergic worsening phenotypic effect.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Female
  • Gene Expression Regulation / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Gestational Age
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Italy
  • Lung / ultrastructure
  • Male
  • Mutation*
  • Pulmonary Surfactant-Associated Protein B / genetics*
  • Pulmonary Surfactant-Associated Protein C / genetics*
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Retrospective Studies

Substances

  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • SFTPC protein, human