ABCD1 p.Ala19Ser
[switch to full view]Comments [show]
None has been submitted yet.
PMID: 23300730
[PubMed]
Amorosi CA et al: "X-linked adrenoleukodystrophy: molecular and functional analysis of the ABCD1 gene in Argentinean patients."
No.
Sentence
Comment
6
In one patient 2 changes were found: a known missense (p.His669Arg) and an unpublished amino acid substitution (p.Ala19Ser).
X
ABCD1 p.Ala19Ser 23300730:6:114
status: NEW7 In vitro studies suggest that p.Ala19Ser is a polymorphism.
X
ABCD1 p.Ala19Ser 23300730:7:32
status: NEW72 Briefly, different degenerate primer pair, introducing point mutation c.55 G.T (p.Ala19Ser), c.1259 A.G (p.His420Pro) or c.1640 A,G (p.Tyr547Cys), were used in a thermal cycling reaction (19 cycles).
X
ABCD1 p.Ala19Ser 23300730:72:82
status: NEW106 Each line was loaded with the same amount of total protein extracts, as verified with anti-b-actin protein. Line 1: healthy fibroblasts, line 2: X-linked adrenoleukodystrophy fibroblasts, line 3: fibroblats expressing wild type ALDP-GFP, line 4: fibroblats expressing ALDP-GFP (c.55G.T, p.Ala19Ser), line 5: fibroblats expressing ALDP-GFP (c.1640A.G, p.Tyr547Cys).
X
ABCD1 p.Ala19Ser 23300730:106:289
status: NEW114 In patient 1 (Table 1), we identified two different substitutions, one in exon 1 and other in exon 10 (p.Ala19Ser and p.His669Arg).
X
ABCD1 p.Ala19Ser 23300730:114:105
status: NEW115 The last one has been identified previously as a disease causing mutation in the X-ALD database (http://www-x-ald.nl), but p.Ala19Ser has not been reported before.
X
ABCD1 p.Ala19Ser 23300730:115:125
status: NEW116 When a construct carrying substitution p.Ala19Ser was transfected into X-ALD fibroblasts, ALDP was detected by western blot analysis (Figure 1) and peroxisomal b-oxidation was restored to control levels (Figure 2).
X
ABCD1 p.Ala19Ser 23300730:116:41
status: NEW117 This demonstrates that the p.Ala19Ser may represent a SNP. As expected, SIFT predicted that p.Ala19Ser is tolerated with a score of 0.05 (Table 2).
X
ABCD1 p.Ala19Ser 23300730:117:29
status: NEWX
ABCD1 p.Ala19Ser 23300730:117:94
status: NEW118 PolyPhen predicted that p.Ala19Ser can be a benign variant although the alanine residue at position 19 it was highly conserved between different species (Figure 5).
X
ABCD1 p.Ala19Ser 23300730:118:26
status: NEW119 Finally, five polymorphisms were detected: 3 novel intronic changes (c.1634+14T.A, c.1992-32C.T and c.55G.T or p.Ala19Ser) and 2 previously reported (c.1548G.A, p.Leu516Leu and c.2019C.T, p.Phe673Phe).
X
ABCD1 p.Ala19Ser 23300730:119:113
status: NEW150 Missense Change p.Ala19Ser p.Tyr547Cys p.His420Pro p.His669Arg p.Ala341Asp Multiple sequence alignment MSA Highly conserved Highly conserved Relatively conserved Conserved Highly conserved http://www.ebi.ac.uk/clustalw2/ SIFT Tolerated Non-tolerated Tolerated Tolerated Non-tolerated http://blocks.fhcrc.org/sift/SIFT.html PolyPhen Benign Probably damaging Probably damaging Benign Possibly damaging http://genetics.bwh.harvard.edu/pph doi:10.1371/journal.pone.0052635.t002 showed that the mutant transcript is not translated (Figure 3); therefore the levels of b-oxidation are deficient (Figure 4).
X
ABCD1 p.Ala19Ser 23300730:150:18
status: NEW154 The bioinformatics studies are predictive; however the results were consistent in most cases with functional studies, except for p.Ala19Ser.
X
ABCD1 p.Ala19Ser 23300730:154:131
status: NEW155 In patient 1 (Table 1) we identified two different one-base substitution, one new in exon 1 (c.55G.T) and one known in exon 10 (c.2006A.G, http://www-x-ald.nl), both of them causing an amino acid change (p.Ala19Ser and p.His669Arg, respectively).
X
ABCD1 p.Ala19Ser 23300730:155:206
status: NEW156 The p.Ala19Ser allele had similar expression and b-oxidation levels to wild type ALDP in the experiments of transient expression in X-ALD fibroblast (Figures 1 and 2).
X
ABCD1 p.Ala19Ser 23300730:156:6
status: NEW158 Besides the fact that p.His669Arg has been found as the only mutation in other patients where no protein was detected in western blot also suggests that p.Ala19Ser is a SNP.
X
ABCD1 p.Ala19Ser 23300730:158:155
status: NEW159 However p.Ala19Ser is highly conserved in all species unlike p.His669 (Figure 6) and both were predicted to be ''bening`` by the Polyphen program and ''tolerated`` by the SIFT program (Table 2).
X
ABCD1 p.Ala19Ser 23300730:159:10
status: NEW