ABCMdb

PMID: 17618459

Yokota T, Matsumura Y, Ban N, Matsubayashi T, Inagaki N
Heterozygous ABCA3 mutation associated with non-fatal evolution of respiratory distress.
Eur J Pediatr. 2008 Jun;167(6):691-3. Epub 2007 Jul 6., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCA3 p.Thr1114Ala ABCA3 p.Trp1148* Analysis of the ATP-binding cassette transporter A3 (ABCA3; OMIM 601615) gene showed a compound heterozygous mutation from paternal W1148X and maternal T1114A. Login to comment 27 ABCA3 p.Thr1114Ala ABCA3 p.Trp1148* Direct sequence analysis of ABCA3 in the patient revealed a compound heterozygous mutation, W1148X on the paternal allele and T1114A on the maternal allele. Login to comment 28 ABCA3 p.Thr1114Ala ABCA3 p.Trp1148* In vitro study showed that the T1114A mutant had moderately preserved ATP-hydrolysis activity (51% of wild type) with normal intracellular localization, while the W1148X mutant had impaired intracellular localization. Login to comment 29 ABCA3 p.Thr1114Ala ABCA3 p.Trp1148* W1148X is a type I, loss-of-function mutation (abnormal intracellular localization) and T1114A is a type II mutation (normal intracellular localization with decreased ATP-hydrolysis activity) [2]. Login to comment 40 ABCA3 p.Gly1221Ser ABCA3 p.Gly1221Ser ABCA3 p.Leu1580Pro ABCA3 p.Leu1580Pro ABCA3 p.Leu982Pro All of the patients reported with fatal surfactant deficiency carrying type I/type II compound heterozygous ABCA3 mutation (L982P/G1221S or Ins1518fs/L1580P) died within the neonatal period [4], and ATP-hydrolysis activity was severely impaired in the case of the G1221S and L1580P mutants [2]. Login to comment 41 ABCA3 p.Thr1114Ala In this case, the moderately preserved ATP-hydrolysis activity of the T1114A mutant may underlie the milder symptoms and later onset of respiratory failure than in fatal newborn surfactant deficiency. Login to comment 42 ABCA3 p.Thr1114Ala Because ATP-hydrolysis activity of ABCA3 protein is regulated by lipids [3], exogenous surfactant lipid itself might rescue the activity of the T1114A mutant protein. Login to comment