ABCA3 p.Arg1561Lys
| Predicted by SNAP2: | A: D (71%), C: D (66%), D: D (71%), E: D (66%), F: D (66%), G: D (71%), H: N (53%), I: D (66%), K: N (66%), L: D (66%), M: D (66%), N: N (53%), P: D (66%), Q: D (53%), S: D (53%), T: N (53%), V: D (66%), W: D (75%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Ultrastructure of lamellar bodies in congenital su... Ultrastruct Pathol. 2005 Nov-Dec;29(6):503-9. Edwards V, Cutz E, Viero S, Moore AM, Nogee L
Ultrastructure of lamellar bodies in congenital surfactant deficiency.
Ultrastruct Pathol. 2005 Nov-Dec;29(6):503-9., [PMID:16316951]
Abstract [show]
Congenital surfactant deficiency (CSD) is a newly identified neonatal lung disorder associated with a variety of molecular defects affecting surfactant synthesis and secretion in alveolar type II cells. The authors present ultrastructural findings of abnormal lamellar bodies in lung biopsies from 4 infants with CSD. All were term infants presenting shortly after birth with severe respiratory failure that was unresponsive to conventional therapy and all died within the first month of life. Lung biopsies were performed between 8 and 25 days of age. Biochemical and molecular studies in 2 unrelated male infants identified SP-B deficiency, one case with 121 ins 2 mutation and the second with a 209 + 4 A > G mutation. Light microscopy in both cases showed features of alveolar proteinosis. Ultrastructurally, alveolar type II cells lacked mature lamellar bodies, and their cytoplasm contained numerous pleomorphic inclusions with membranous and vesicular structures not seen in normal type II cells. The other 2 infants were a pair of siblings in whom molecular studies identified mutations in ABCA3 transporter gene. Light microscopy showed features of acinar dysplasia and desquamative interstitial pneumonitis. TEM studies revealed absence of mature lamellar bodies in type II cells and instead showed a mixture of cytoplasmic electron-dense inclusions with concentric membranes and distinctive electron dense aggregates. The ultrastructural changes in alveolar type II cells correlated well with specific gene defect. In SP-B deficiency, the absence of mature lamellar bodies is consistent with the postulated role for this protein in the formation of lamellar bodies. The lack of mature lamellar bodies in the ABCA3 gene mutations is due to the dysfunction of this endogenous lipid transporter that targets surfactant lipid moieties to the lamellar bodies. The findings demonstrate the importance of TEM studies of lung biopsies from infants with CSD as it is a critical adjunct in the diagnosis of neonatal lung disease and in defining the underlying cellular defects.
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No. Sentence Comment
54 Note the random lamellae and the associated membranous and vesicular structures within composite bodies and abnormally large vesicular body (Ã ), Â30,000. mutation in coding exon 8 (A > G); nonsense mutation in coding exon 27, R1561K [8].
X
ABCA3 p.Arg1561Lys 16316951:54:239
status: NEW