ABCMdb

ABCD1 p.Arg591Gln

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Publications

PMID: 11748843 [PubMed] Kemp S et al: "ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations."

No. Sentence Comment

259 For example, two disease-causing missense mutations, P484R and R591Q. Login to comment

PMID: 10551832 [PubMed] Liu LX et al: "Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters."

No. Sentence Comment

47 ALD point mutations (R389H, R401Q, P484R, and R591Q) were individually introduced into pGBT- and pLEX-hALDPc by site-directed mutagenesis using "overlap extension PCR" with Pfu polymerase (Stratagene) and appropriate primers (25). Login to comment
72 These mutations (R389H, R401Q, P484R, and R591Q) were generated as described above and tested in two-hybrid assays. Login to comment
73 The P484R mutation leads to a decreased amount of ALDP in patient fibroblasts,3 whereas the three other mutations have no effect on ALDP stability in vivo (28-31). Login to comment
74 Our results show that the mutations R389H and R401Q had no effect on the interactions of hALDPc with itself (Fig. 2A, rows 1, 3, and 5), mALDRPc (Fig. 2B, rows 1, 3, and 5), or hPMP70c (Fig. 2C, rows 1, 3, and 5). Login to comment
75 In contrast, the P484R and R591Q mutations 2 L. X. Liu, K. Janvier, V. Berteaux-Lecellier, N. Cartier, R. Benarous, and P. Aubourg, unpublished results. Login to comment
90 B and C, interactions of wild type and mutated (R389H, R401Q, P484R, and R591Q) ALDPc with mALDRPc and hPMP70c. Login to comment
95 A, HF7c yeast strains expressing wild type or mutated (R389H, R401Q, P484R, and R591Q) ALDPc fused to Gal4-BD were analyzed for histidine auxotrophy (left panel, medium with histidine; right panel, medium without histidine). Login to comment
152 In contrast, the R591Q disease mutation, which alters the dimerization of ALDP in the yeast two-hybrid assays, does not lead to ALDP unstability in vivo. Login to comment
46 ALD point mutations (R389H, R401Q, P484R, and R591Q) were individually introduced into pGBT- and pLEX-hALDPc by site-directed mutagenesis using "overlap extension PCR" with Pfu polymerase (Stratagene) and appropriate primers (25). Login to comment
71 These mutations (R389H, R401Q, P484R, and R591Q) were generated as described above and tested in two-hybrid assays. Login to comment
89 B and C, interactions of wild type and mutated (R389H, R401Q, P484R, and R591Q) ALDPc with mALDRPc and hPMP70c. Login to comment
94 A, HF7c yeast strains expressing wild type or mutated (R389H, R401Q, P484R, and R591Q) ALDPc fused to Gal4-BD were analyzed for histidine auxotrophy (left panel, medium with histidine; right panel, medium without histidine). Login to comment
151 In contrast, the R591Q disease mutation, which alters the dimerization of ALDP in the yeast two-hybrid assays, does not lead to ALDP unstability in vivo. Login to comment
45 ALD point mutations (R389H, R401Q, P484R, and R591Q) were individually introduced into pGBT- and pLEX-hALDPc by site-directed mutagenesis using "overlap extension PCR" with Pfu polymerase (Stratagene) and appropriate primers (25). Login to comment
70 These mutations (R389H, R401Q, P484R, and R591Q) were generated as described above and tested in two-hybrid assays. Login to comment
88 B and C, interactions of wild type and mutated (R389H, R401Q, P484R, and R591Q) ALDPc with mALDRPc and hPMP70c. Login to comment
93 A, HF7c yeast strains expressing wild type or mutated (R389H, R401Q, P484R, and R591Q) ALDPc fused to Gal4-BD were analyzed for histidine auxotrophy (left panel, medium with histidine; right panel, medium without histidine). Login to comment
150 In contrast, the R591Q disease mutation, which alters the dimerization of ALDP in the yeast two-hybrid assays, does not lead to ALDP unstability in vivo. Login to comment

PMID: 9212180 [PubMed] Imamura A et al: "Two novel missense mutations in the ATP-binding domain of the adrenoleukodystrophy gene: immunoblotting and immunocytological study of two patients."

No. Sentence Comment

62 The immunofluorescence study has revealed positive immunoreactivity with anti-ALD protein antibody in a pathogenic ALD mutant, R591Q, between the Walker A and B motifs (Watkins et al. 1995),while ALD protein was not detectable in ALD protein mutants. Login to comment

PMID: 16949688 [PubMed] Berger J et al: "X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects."

No. Sentence Comment

94 Two X-ALD disease mutations located in the C-terminal half of ALDP (P484R and R591Q) affect both homo- and heterodimerization of ALDP [40]. Login to comment

PMID: 17542813 [PubMed] Takahashi N et al: "Adrenoleukodystrophy: subcellular localization and degradation of adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense mutations."

No. Sentence Comment

238 Actually, in their experiments the mutation of P484R and R591Q reduced the interaction of the COOH-terminal half of ALDP. Login to comment

PMID: 12530690 [PubMed] Gartner J et al: "Functional characterization of the adrenoleukodystrophy protein (ALDP) and disease pathogenesis."

No. Sentence Comment

41 The mutant constructs included missense mutations of patients with X-ALD in the nucleotide binding fold regions Walker A and 19mer (ALDP-NBF-G512S, ALDP-NBF-Q544R, ALDP-NBF-P560L, ALDP-NBF-R591Q, ALDP-NBF-S606L, and ALDP-NBF-D629H) and corresponding mutations in another ABC transporter in the peroxisome membrane, the 70 kDa peroxisomal membrane protein (PMP70; PMP70-NBF-G478R, PMP70- NBF-S572I). Login to comment

PMID: 7668254 [PubMed] Watkins PA et al: "Altered expression of ALDP in X-linked adrenoleukodystrophy."

No. Sentence Comment

176 In 11 patients, missense mutations that occurred throughout the protein were found: within the transmembrane domains (patients 1, 3, and 4), within the ATP-binding domain (patients 8-12), and on either side of the ATP-binding Table 3 Mutational Analysis of the ALD Gene in IS Unrelated Patients ALDP Patient Phenotype Mutation Consequence Immunoreactivity 1 .................. CALD 825 A-GG K276E + 2.................. AMN 870-2AGAGE291,& 3 .................. CALD 872 G-C E291D 4 .................. AMN 1023 T-IC S342P+ 5 .................. AMN 1166 G-C R389H + 6 .................. CALD 1201 G-AA R401Q + 7 ........ CALD 1415-6 AAG FS@472 8 ........ AMN 1771 G-AA R591Q + 9 ........ Addison 1817 C-T S606L + 10 ................ AMN 1850 G-AA R617H 11 ................ CALD 1876 G-AA A626T 12 ................ Fetus 1884 G-C D629H + 13 ................ CALD 1932 C-UT Q645X 14 ................ AMN 1978 C-OT R660W 15 ........ AMN AExon7-10 Null Mutations in the ALD gene were determined, as described in Methods, in 15 of the ALD patients reported in table 2. Login to comment
178 In 11 patients, missense mutations that occurred throughout the protein were found: within the transmembrane domains (patients 1, 3, and 4), within the ATP-binding domain (patients 8-12), and on either side of the ATP-binding Table 3 Mutational Analysis of the ALD Gene in IS Unrelated Patients ALDP Patient Phenotype Mutation Consequence Immunoreactivity 1 .................. CALD 825 A-GG K276E + 2 .................. AMN 870-2 AGAG E291,& 3 .................. CALD 872 G-C E291D 4 .................. AMN 1023 T-IC S342P + 5 .................. AMN 1166 G-C R389H + 6 .................. CALD 1201 G-AA R401Q + 7 ........ CALD 1415-6 AAG FS@472 8 ........ AMN 1771 G-AA R591Q + 9 ........ Addison 1817 C-T S606L + 10 ................ AMN 1850 G-AA R617H 11 ................ CALD 1876 G-AA A626T 12 ................ Fetus 1884 G-C D629H + 13 ................ CALD 1932 C-UT Q645X 14 ................ AMN 1978 C-OT R660W 15 ........ AMN AExon7-10 Null Mutations in the ALD gene were determined, as described in Methods, in 15 of the ALD patients reported in table 2. Login to comment

PMID: 9425230 [PubMed] Braiterman LT et al: "Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteins."

No. Sentence Comment

184 Mutant ALDP cDNAs were generated by TA cloning (Invitrogen) of RT-PCR products generated from RNA isolated from patient fibroblast cell lines harboring either the R617H mutation that both destablizes and inactivates ALDP or the missense mutation R591Q that inactivates ALDP without altering stability of the protein (5). Login to comment
183 Mutant ALDP cDNAs were generated by TA cloning (Invitrogen) of RT-PCR products generated from RNA isolated from patient fibroblast cell lines harboring either the R617H mutation that both destablizes and inactivates ALDP or the missense mutation R591Q that inactivates ALDP without altering stability of the protein (5). Login to comment
185 Mutant ALDP cDNAs were generated by TA cloning (Invitrogen) of RT-PCR products generated from RNA isolated from patient fibroblast cell lines harboring either the R617H mutation that both destablizes and inactivates ALDP or the missense mutation R591Q that inactivates ALDP without altering stability of the protein (5). Login to comment

PMID: 22280810 [PubMed] Salsano E et al: "Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms."

No. Sentence Comment

53 All samples were tested in Table 1 Clinical Findings, Genotype, X-Chromosome Inactivation (XCI), ABCD1 Allele-Specific Expression (ASE) and Biochemical Findings (VLCFA plasma levels) of X-ALD carriers Nr of family, consultants Age (yrs) Presence of symptoms (age at onset, yrs) Mutations XCI pattern ABCD1 ASE (mut:wt) C26 (nv) C26/C22 (nv) C24/C22 (nv) F1 II-3 67 Yes (45) 410G > A W137X 97:03 84:16 1,09 (<0,75) 48 (<17) 1644 (<1100) F1 III-2 34 No 410G > A W137X 91:09 nd 0,58 (<0,75) 47 (<17) 1482 (<1100) F2 I-2 61 Yes (59) 427C > G P143A 71:29 93:07 0,85 (<0,75) 18 (<17) 1222 (<1100) F2 II-1 38 No 427C > G P143A 85:15 83:17 nd nd nd F2 II-2 35 No 427C > G P143A 76:24 77:23 nd nd nd F3 II-2 73 Yes (45) 428C > A P143H 60:40 38:62 1,45 (<1,50) 28 (<40) 700 (<820) F3 III.1 46 No 428C > A P143H 84:16 84:16 1,53 (<1,50) 40 (<40) 860 (<820) F3 III-2 50 No 428C > A P143H 83:17 75:25 1,75 (<1,50) 37 (<40) 733 (<820) F4 II-3 75 Yes (50) 652C > T; 664G > T P218S; V222L 81:19 82:18 1,57 (<0,75) 19 (<17) 1680 (<1100) F4 III-1 44 No 652C > T; 664G > T P218S; V222L 83:17 81:19 2,38 (<1,50) 53 (<40) 1424 (<820) F4 III-3 45 Yes (29) 652C > T; 664G > T P218S; V222L 89:11 82:18 1,00 (<0,75) 36 (<17) 1611 (<1100) F5 II-1 55 Yes (54) 1202G > A R401Q 98:02 82:18 1,96 (<1,50) 38 (<40) 1031 (<820) F6 II-1 76 Yes (58) 1727T > C L576P 73:27 76:24 2,10 (<0,75) 21 (<17) 1039 (<1100) F7 I-2 72 No 1772G > A R591Q n/a n/a 1,23 (<1,5) 16 (<40) 798 (<820) F7 II-1 44 Yes (34) 1772G > A R591Q 96:04 97:03 2,7 (<1,50) 56 (<40) 957 (<820) F8 II-1 62 Yes (40) 1992G > A W664X 83:17 82:18 3,08 (<1,50) 56 (<40) 1132 (<820) F9 II-1 63 No 293C > T S98L 83:17 93:07 1,82 (<1,50) 37 (<40) 888 (<820) F9 II-3 57 No 293C > T S98L 79:21 75:25 1,99 (<1,50) 42 (<40) 913 (<820) F9 III-2 20 No 293C > T S98L 75:25 61:39 2,65 (<1,50) 46 (<40) 1149 (<820) F10 I-2 63 No 443A > G N148S 86:14 42:58 2,16 (<1,50) 42 (<40) 788 (<820) F10 II-2 40 No 443A > G N148S 96:04 84:16 2,17 (<1,50) 43 (<40) 757 (<820) F11 III-1 67 No 1165C > T R389C 52:48 72:28 0,7 (<1,50) 13 (<40) 572 (<820) F11 III-3 64 No 1165C > T R389C 78:22 34:66 1,1 (<1,50) 16 (<40) 823 (<820) F11 III-5 49 No 1165C > T R389C 98:02 20:80 1,05 (<1,50) 16 (<40) 848 (<820) F11 III-6 46 No 1165C > T R389C 71:29 74:26 1,30 (<1,50) 18 (<40) 1000 (<820) F11 V-1 26 No 1165C > T R389C 57:43 58:42 0,68 (<1,50) 14 (<40) 663 (<820) F12 I-2 53 No 1211C > A S404X 95:05 09:91 nd nd nd F13 I-2 60 No del. ex8-10 n/a 76:24 nd nd nd nd duplicate and one male DNA sample was included in each experiment as a control for enzymatic digestion. Login to comment

PMID: 23566833 [PubMed] Niu YF et al: "ABCD1 mutations and phenotype distribution in Chinese patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

74 Exon Nucleotide change Amino acid change Phenotype P1 None None None CCALD P2 7 c.1661G>A p.Arg554His CCALD P3 5 c.1477_1488 + 11del 23 p.Leu493_Arg496del Adolescent ALD P4 2 c.1028G>T p.Gly343Val CCALD P5 6 c.1553G>A p.Arg518Gln CCALD P6 5 c.1415_16delAG p.Gln472fsX83 CCALD P7 6 c.1534G>A p.Gly512Ser Adolescent ALD P8 7 c.1679C>T p.Pro560Leu CCALD P9 7 c.1772G>A p.Arg591Gln ACALD P10 5 c.1415_16delAG p.Gln472fsX83 ACALD Fig. 1. Login to comment