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Surfactant deficiency syndrome in an infant with a C‐terminal frame shift in ABCA3: A case report
Author(s) -
Akil Nour,
Fischer Anthony J.
Publication year - 2018
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.23994
Subject(s) - lamellar granule , mutation , medicine , neonatal respiratory distress syndrome , pulmonary surfactant , amino acid , biochemistry , biology , genetics , gene , pregnancy , gestational age
Deficiency in ATP binding cassette A3 (ABCA3) causes neonatal respiratory distress, hypoxemic respiratory failure, and interstitial lung disease. ABCA3 transports phospholipids into the lamellar bodies of type II alveolar cells, a critical step in alveolar surfactant production. We report a term infant with ABCA3 surfactant deficiency syndrome with the E292V (c.875A>T; p.Glu292Val) mutation in trans with a novel C‐terminal frame shift mutation (c.4938delC; p.Met1647fs). This mutation removes the final 58 amino acids and substitutes 33 incorrect amino acids. The frame shift spares membrane spanning and nucleotide binding domains, but disrupts a highly conserved C‐terminal domain, which includes sequence motifs necessary for the function of human paralogs ABCA1, ABCA4, and the bacterial homolog DrrA. This observation suggests the C‐terminal domain is also required for normal function of ABCA3.