ABCC7 p.Glu60Ala
| ClinVar: |
c.178G>T
,
p.Glu60*
D
, Pathogenic
|
| CF databases: |
c.178G>T
,
p.Glu60*
D
, CF-causing
c.178G>A , p.Glu60Lys (CFTR1) ? , This mutation was found by DGGE and direct DNA sequencing in a CF child who carries the DI507 in paternal CF chromosome. The patient is 5 years old, PS and sweat test 80mEq/l. Her healthy sister carries the DI507 mutation.(Original Note - Casals et al., 2August2000) The mutation was also reported by Claustres et al., 16November2000 This putative mutation was also detected by DGGE and identified by DNA fluorescent sequencing in an young CF patient from Southern France. She carries the mutation 2790-1G->C on the other chromosome. |
| Predicted by SNAP2: | A: D (63%), C: D (63%), D: D (66%), F: D (71%), G: D (75%), H: D (71%), I: D (75%), K: D (80%), L: D (75%), M: D (71%), N: D (71%), P: D (85%), Q: D (66%), R: D (80%), S: D (71%), T: D (71%), V: D (71%), W: D (75%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: N, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Rescuing cystic fibrosis transmembrane conductance... Proc Natl Acad Sci U S A. 2004 May 25;101(21):8221-6. Epub 2004 May 12. Cormet-Boyaka E, Jablonsky M, Naren AP, Jackson PL, Muccio DD, Kirk KL
Rescuing cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by transcomplementation.
Proc Natl Acad Sci U S A. 2004 May 25;101(21):8221-6. Epub 2004 May 12., 2004-05-25 [PMID:15141088]
Abstract [show]
Most cases of cystic fibrosis (CF) are caused by mutations that block the biosynthetic maturation of the CF gene product, the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR-processing mutants fail to escape the endoplasmic reticulum and are rapidly degraded. Current efforts to induce the maturation of CFTR mutants target components of the biosynthetic pathway (e.g., chaperones) rather than CFTR per se. Such methods are inherently nonspecific. Here we show that the most common CF-causing mutant (DeltaF508-CFTR) can form mature, functional chloride channels that reach the cell surface when coexpressed with several other CFTR-processing mutants or with amino fragments of the wild-type CFTR protein. This transcomplementation effect required a specific match between the region flanking the disease-causing mutation and the complementing fragment; e.g., amino fragments complemented DeltaF508-CFTR but not H1085R (a carboxy-processing mutant), whereas a carboxy fragment complemented H1085R but not DeltaF508-CFTR. Transcomplementing fragments did not affect CFTR interactions with Hsc70, a chaperone previously implicated in CFTR biosynthesis. Instead, they may promote CFTR maturation by blocking nonproductive interactions between domains within the same or neighboring CFTR polypeptides that prevent normal processing. These findings indicate that it may be possible to develop CF therapies (e.g., mini-cDNA constructs for gene therapy) that are tailored to specific disease-causing mutants of CFTR.
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No. Sentence Comment
80 Figs. 1 D and E show that the steady-state amount of mature ⌬F508-CFTR protein can be enhanced substantially by coexpressing this mutant with the N-tail processing mutants (e.g., E60A-CFTR) in COS-7 cells by using a strong viral expression system (vaccinia virus).
X
ABCC7 p.Glu60Ala 15141088:80:186
status: NEW