Exome sequencing of extreme phenotypes in bronchopulmonary dysplasia

Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants with growing evidence that genetic factors contribute largely to moderate and severe cases. We assessed by exome sequencing if rare genetic variants could account for extremely severe phenotypes. We selected 6 infants born very preterm with severe bronchopulmonary dysplasia and 8 very preterm born controls for exome sequencing. We filtered whole exome sequencing results to include only rare variants and selected variants and/or genes with variants that were present in at least 2 cases and absent in controls. We selected variants, all heterozygous, in 9 candidate genes, 7 with a putative role in lung development and 2 that displayed 3 variations in 3 different cases, independently of their potential role in lung development. Sequencing of 5 other severe cases for these variants did not replicate our results.