Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter

• DOI: 10.1101/mcs.a005074
• Publication Date: 2020-06-12T23:07:54Z
• Authors: Zoltán N. Oltvai; Eric A. Smith; Katie Wiens; Lawrence M. Nogee; Mark Luquette; Andrew C. Nelson; Kathryn A. Wikenh...
• Keywords: Compound heterozygosity; Lamellar granule

The ATP-binding cassette transporter member A3 (ABCA3) is a lipid with critical function in pulmonary surfactant biogenesis. Biallelic loss-of-function mutations ABCA3 result severe deficiency leading to neonatal respiratory failure death the first year of life. Herein, we describe newborn distress at birth progressing requiring transplant. This patient was found have maternally inherited frameshift mutation and paternally synonymous variant predicted create cryptic splice site. Additional studies showed reduced expression hyperplastic alveolar epithelial type II cells lamellar body alterations characteristic deficiency, diagnosis autosomal recessive ABCA3-related dysfunction. case highlights need for an integrated, comprehensive approach diseases when silico modeling utilized interpretation key novel genetic mutations.