ABCMdb

PMID: 17597647

Bullard JE, Nogee LM
Heterozygosity for ABCA3 mutations modifies the severity of lung disease associated with a surfactant protein C gene (SFTPC) mutation.
Pediatr Res. 2007 Aug;62(2):176-9., [PubMed]

Sentences

No. Mutations Sentence Comment

44 ABCA3 p.Glu292Val The restriction endonuclease BsrGI was purchased from New England Biolabs (Beverly, MA) and used according to manufacturer`s specifications for analysis of ABCA3 E292V, as reported previously (23). Login to comment 48 ABCA3 p.Glu292Val ABCA3 E292V was assayed for in the 19 children because of its association with multiple unrelated children and lung disease (23). Login to comment 49 ABCA3 p.Glu292Val Two infants were identified with ABCA3 E292V and had the onset of their symptoms at younger than 2 mo of age. Login to comment 53 ABCA3 p.Glu292Val Sequencing confirmed that patients 1 and 2 had the ABCA3 E292V mutation and no other mutation. Login to comment 54 ABCA3 p.Leu212Met ABCA3 p.Leu212Met Patient 3 was heterozygous for a missense mutation in exon 8, a substitution of methionine for leucine at codon 212, L212M. Login to comment 67 ABCA3 p.Glu292Val ABCA3 p.Leu212Met Circle, female; square, male; shaded quarter symbol, SFTPC I73T; solid quarter symbol, ABCA3 E292V; check- ered quarter symbol, ABCA3 L212M; slash through symbol, deceased; IPF, idiopathic pulmonary fibrosis; RSV, respiratory syncytial virus. Login to comment 72 ABCA3 p.Glu292Val Two of the four infants had ABCA3 E292V, a mutation that has been associated with pILD (23). Login to comment 73 ABCA3 p.Glu292Val The population frequency of ABCA3 E292V is low, approximately one in 275 individuals (personal communication, T. Garmany and A. Hamvas). Login to comment 74 ABCA3 p.Glu292Val Thus, the finding of ABCA3 E292V in two of the 19 patients with SFTPC I73T seems unlikely to have occurred by chance. Login to comment 75 ABCA3 p.Glu292Val ABCA3 p.Leu212Met The third infant had a different missense mutation, ABCA3 L212M, which results in a conservative neutral substitution. Login to comment 76 ABCA3 p.Leu212Met ABCA3 p.Leu212Met It is possible that L212M represents a rare but benign polymorphism. Login to comment 77 ABCA3 p.Arg106* ABCA3 p.Leu212Met ABCA3 p.Leu212Met ABCA3 p.Leu212Met However, two siblings with significant respiratory symptoms and who had lung histopathology findings consistent with surfactant dysfunction were compound heterozygotes for a previously identified ABCA3 nonsense mutation (R106X) and L212M, suggesting that L212M is a disease-causing mutation (L.M. Nogee, unpublished data). Login to comment 78 ABCA3 p.Arg106* ABCA3 p.Leu212Met ABCA3 p.Leu212Met However, two siblings with significant respiratory symptoms and who had lung histopathology findings consistent with surfactant dysfunction were compound heterozygotes for a previously identified ABCA3 nonsense mutation (R106X) and L212M, suggesting that L212M is a disease-causing mutation (L.M. Nogee, unpublished data). Login to comment