ABCMdb

PMID: 17095348

Prestridge A, Wooldridge J, Deutsch G, Young LR, Wert SE, Whitsett JA, Nogee L
Persistent tachypnea and hypoxia in a 3-month-old term infant.
J Pediatr. 2006 Nov;149(5):702-706., [PubMed]

Sentences

No. Mutations Sentence Comment

65 ABCA3 p.Arg20Leu ABCA3 p.Arg20Leu No deviations from the known SFTPB or SFTPC sequences were identified; however, the sequence analysis of ABCA3 revealed 2 previously unreported mutations: a heterozygous G&#a1;T transversion in exon 5 at cDNA position 59, resulting in a nonconservative substitution of leucine for arginine in codon 20 (R20L), and a heterozygous 25-base pair deletion in exon 29 (4483del25) resulting in a frame shift. Login to comment 66 ABCA3 p.Arg20Leu ABCA3 p.Arg20Leu ABCA3 p.Arg20Leu No deviations from the known SFTPB or SFTPC sequences were identified; however, the sequence analysis of ABCA3 revealed 2 previously unreported mutations: a heterozygous G¡T transversion in exon 5 at cDNA position 59, resulting in a nonconservative substitution of leucine for arginine in codon 20 (R20L), and a heterozygous 25-base pair deletion in exon 29 (4483del25) resulting in a frame shift. Login to comment 67 ABCA3 p.Arg20Leu Paternal DNA was not available for analysis; analysis of maternal DNA demonstrated heterozygosity for the R20L mutation but not for the 4483del25 mutation, indicating that these mutations were likely on separate alleles in the child. Login to comment 77 ABCA3 p.Glu292Val contain more densely packed membranes with eccentrically placed, electron-dense inclusion bodies.20,21 Histological evaluation of the lung in patients with mutations in ABCA3 reveals diffuse hyperplasia of alveolar type II cells and accumulation of proteinaceous material in distal air spaces.21 ABCA3 mutations were first identified in neonates with severe lung disease whose lung histopathology findings were consistent with some forms of ILD, as well as with inheritance of the disorder as an autosomal recessive condition.21 In a subsequent study, older children with histopathology diagnoses of ILD were found to have ABCA3 mutations, particularly a missense mutation, E292V.28 Presumably decreased but not complete loss of function of the ABCA3 protein accounted for the milder phenotype than that seen in the neonates. Login to comment 78 ABCA3 p.Glu292Val contain more densely packed membranes with eccentrically placed, electron-dense inclusion bodies.20,21 Histological evaluation of the lung in patients with mutations in ABCA3 reveals diffuse hyperplasia of alveolar type II cells and accumulation of proteinaceous material in distal air spaces.21 ABCA3 mutations were first identified in neonates with severe lung disease whose lung histopathology findings were consistent with some forms of ILD, as well as with inheritance of the disorder as an autosomal recessive condition.21 In a subsequent study, older children with histopathology diagnoses of ILD were found to have ABCA3 mutations, particularly a missense mutation, E292V.28 Presumably decreased but not complete loss of function of the ABCA3 protein accounted for the milder phenotype than that seen in the neonates. Login to comment 81 ABCA3 p.Arg208Trp ABCA3 p.Met760Arg Subsequent analysis of archived lung tissue indicated that the child was a compound heterozygote for 2 ABCA3 missense mutations (R208W and M760R), finally establishing a specific etiologic cause for the child`s lung disease. Login to comment 82 ABCA3 p.Arg208Trp ABCA3 p.Met760Arg Subsequent analysis of archived lung tissue indicated that the child was a compound heterozygote for 2 ABCA3 missense mutations (R208W and M760R), finally establishing a specific etiologic cause for the child`s lung disease. Login to comment