ABCMdb

ABCD1 p.Arg660Trp

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Publications

PMID: 8651290 [PubMed] Feigenbaum V et al: "Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy."

No. Sentence Comment

59 Twenty-nine different mutations were found, and five of them were present in more than one family (S98L, R518W, and R660W in two families, and 1801 delAG and P560L in four families each). Login to comment
76 58:1135-1144, 1996 Table 2 Mutations in the ALD Gene in Studied Patients AMINO ACID MUTATIONSb HOMOLOGUE INd KINDRED CLINICAL LOCALIZATION AMINO ACID ALDP BY NUMBER PHENOTYPEa DNA CpG Exon IN PROTEINC ALTERATION h/m ALDRP hPMP70 IF/WB' CALD, AMN CALD CALD CALD, AS AD CALD, AMN CALC AD AD AD ALMD CALD CALD, AMN CALD CALD, AMN, AD AMN ALMD CALD ALMD CALD AMN ALD AD, AMN, AS CALD, AS CALD CALD AD CALD AMN, ALMD CALD CALD AMN, ALMD CALD CALD, AMN, ALMD CALD CALD, ALMD, AS ALMD CALD AMN CALD, AMN AD AD AMN CALD G416A Ins T524 C679T C679T C700T C709G G732A A829G C840T Del TA927-28 A928G A985T A1048G DeIGC1080-81 C1174T G1266A ins C1521 1636delC DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 ins TGG 1848 G 1920 A C1938T C1938T G1950A C2065T C2065T C2065T C2065T C2065G G 2166+1 A T2202C DelGC 2335 C2364T C2364T No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found 1 1 + 1 + 1 1 1 + 1 1 + 1 1 1 1 1 1 1 + 1 3 4 S 5 S S S 6 + 6 + 6 6 + 7 + 7 + 7 + 7 + 7 + 7 8 9 9 9 W10 X Frameshift at L46 TMS2 S98L TMS2 S98L T1OSI S108W G116R TMS3 N148S TMS3 R152C Frameshift at Y180 Y181C TMS4 D200V TMS4 D221G Frameshift at R231 P263L EAA-like A294T Frameshift at V378 Frameshift at T416 Frameshift at E471 Frameshift at E471 Frameshift at E471 Frameshift at E471 ins val 491 Walker A G512S Walker A R518W Walker A R518W G 522 W P560L P560L P560L P560L P56OR Splice at G593 Walker B S606P Frameshift at D649 R660W R660W Absent Not done S A Present S A Present T T Absent S D Decreased G T Absent N N Present R K Present Absent Y Y Not done D D Not done D D Absent Absent P R Decreased A A Not done Absent Absent Absent Absent Absent Absent Absent G G Absent R R Absent R R Decreased G E Absent P P Decreased P P Decreased P P Decreased P P Absent P P Absent Not done S S Absent Absent R R Absent R R Absent Not done Absent Absent Absent Present Absent Absent a CALD = cerebral ALD (5-15 years); AMN = adrenomyeloneuropathy; ALMD = adrenomyeloneuropathy with cerebral involvement; AD = Addison disease; AS = Asymptomatic. Login to comment
92 F, ALD white blood cells (R660W mutation) immunostained with mAb 2B4, showing the absence of ALDP immunoreactivity. Login to comment
131 Lane 1, protein markers; lane 2, control; lane 3, patient 18 (S108W); lane 4, patient 32 (P263L); lane 5, patient 5 (P560L); lane 6, patient 4 (G116R); lane 7, patient 19 (D221G); lane 8, patient 33 (S98L); lane 9, patient 78 (S606P); lane 10, patient 3 (no mutation found); lane 11, patient 37 (P560L); lane 12, patient 22 (R660W); lane 13, control; lane 14, patient 39 (T1051); lane 15, patient 4 (G116R); lane 16, patient 43 (frameshift at Y180); lane 17, patient 5 (P560L); lane 18, patient 59 (G512S); lane 19, patient 29 (frameshift at D649); lane 20, patient 69 (P560L); lane 21, patient 19 (D221G); lane 22, patient 64 (W1OX); lane 23, patient 63 (frameshift at R231); lane 24, patient 52 (no mutation found); lane 25, patient 61 (frameshift at E471); and lane 26, patient 83 (G522W). Login to comment
134 Exceptions are a dinucleotide deletion (del 1801-1802) and P560L missense mutation, which were both observed in four kindreds, and S98L, R518W, and R660W missense mutations, which were each observed in two kindreds. Login to comment
140 In all cases, only one alteration was found, and except for the S98L, R518W, P560L, and R660W mutations, these alterations differed from each other. Login to comment
58 Twenty-nine different mutations were found, and five of them were present in more than one family (S98L, R518W, and R660W in two families, and 1801 delAG and P560L in four families each). Login to comment
75 58:1135-1144, 1996 Table 2 Mutations in the ALD Gene in Studied Patients AMINO ACID MUTATIONSb HOMOLOGUE INd KINDRED CLINICAL LOCALIZATION AMINO ACID ALDP BY NUMBER PHENOTYPEa DNA CpG Exon IN PROTEINC ALTERATION h/m ALDRP hPMP70 IF/WB' CALD, AMN CALD CALD CALD, AS AD CALD, AMN CALC AD AD AD ALMD CALD CALD, AMN CALD CALD, AMN, AD AMN ALMD CALD ALMD CALD AMN ALD AD, AMN, AS CALD, AS CALD CALD AD CALD AMN, ALMD CALD CALD AMN, ALMD CALD CALD, AMN, ALMD CALD CALD, ALMD, AS ALMD CALD AMN CALD, AMN AD AD AMN CALD G416A Ins T524 C679T C679T C700T C709G G732A A829G C840T Del TA927-28 A928G A985T A1048G DeIGC1080-81 C1174T G1266A ins C1521 1636delC DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 ins TGG 1848 G 1920 A C1938T C1938T G1950A C2065T C2065T C2065T C2065T C2065G G 2166+1 A T2202C DelGC 2335 C2364T C2364T No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found 1 1 + 1 + 1 1 1 + 1 1 + 1 1 1 1 1 1 1 + 1 3 4 S 5 S S S 6 + 6 + 6 6 + 7 + 7 + 7 + 7 + 7 + 7 8 9 9 9 W10 X Frameshift at L46 TMS2 S98L TMS2 S98L T1OSI S108W G116R TMS3 N148S TMS3 R152C Frameshift at Y180 Y181C TMS4 D200V TMS4 D221G Frameshift at R231 P263L EAA-like A294T Frameshift at V378 Frameshift at T416 Frameshift at E471 Frameshift at E471 Frameshift at E471 Frameshift at E471 ins val 491 Walker A G512S Walker A R518W Walker A R518W G 522 W P560L P560L P560L P560L P56OR Splice at G593 Walker B S606P Frameshift at D649 R660W R660W Absent Not done S A Present S A Present T T Absent S D Decreased G T Absent N N Present R K Present Absent Y Y Not done D D Not done D D Absent Absent P R Decreased A A Not done Absent Absent Absent Absent Absent Absent Absent G G Absent R R Absent R R Decreased G E Absent P P Decreased P P Decreased P P Decreased P P Absent P P Absent Not done S S Absent Absent R R Absent R R Absent Not done Absent Absent Absent Present Absent Absent a CALD = cerebral ALD (5-15 years); AMN = adrenomyeloneuropathy; ALMD = adrenomyeloneuropathy with cerebral involvement; AD = Addison disease; AS = Asymptomatic. Login to comment
91 F, ALD white blood cells (R660W mutation) immunostained with mAb 2B4, showing the absence of ALDP immunoreactivity. Login to comment

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

174 P560S 7 1678C>T n.d. # P560L 7 1679C>T Reduced P560L 7 1679C>T Reduced fs I588 7 1765delC n.d. # R591P 7 1772G>C Absent S606L 8 1817C>T Present E609K 8 1825G>A Absent E609K 8 1825G>A Absent R617C 8 1849C>T Absent R617H 8 1850G>A Absent R617H 8 1850G>A Absent A626T 9 1876G>A Absent A626T 9 1876G>A Absent A626D 9 1877C>A n.d. # E630G 9 1889A>G n.d. # C631Y 9 1892G>A n.d. # T632I 9 1895C>T n.d. # V635M 9 1903G>A n.d. # L654P 9 1961T>C Absent # R660W 9 1978C>T Absent fs L663 9 1988insT n.d. # fs L663 IVS 9 IVS9+1g>a n.d. # fs L663 IVS 9 IVS9-1g>a n.d. # H667D 10 1999C>G Absent # T668I 10 2003C>T Absent # T693M 10 2078C>T Present # exon1-5del 1-5 n.d. # The 47 mutations marked with a # are novel unique mutations reported for the first time in this paper. Login to comment

PMID: 20661612 [PubMed] Matsukawa T et al: "Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes."

No. Sentence Comment

84 Interestingly, the five previously described SNPs (rs17782508, rs2301345, rs4148077, rs4148078, and rs3742801) that are in complete linkage disequilibrium were significantly less frequently represented in the patients with Japanese AMN than in the controls in the Japanese population (p=0.0468), whereas Table 2 Identified ABCD1 mutations: mutations of ABCD1 that result in amino acid substitutions or in-frame deletions Patient number Phenotype Mutation of ABCD1 Effect of mutation of ABCD1 Position of mutation 13 CCALD 709C>T S108L Loop1 14 CCALD 709C>T S108L Loop1 15 CCALD 829A>G N148S TM2 16 CCALD 1026A>G N214D TM3 17 CCALD 1182G>A G266R Between TM4 and EAA-like 18 CCALD 1324T>Ca L313P Between EAA-like and TM5 19 CCALD 1938C>T R518W Walker A 20 CCALD 1939G>A R518Q Walker A 21 CCALD 2017A>G Q544R Between Walker A and Cons 22 CCALD 2017A>G Q544R Between Walker A and Cons 23 CCALD 2065C>T P560L Between Walker A and Cons 24 CCALD 2065C>T P560L Between Walker A and Cons 25 CCALD Del. 2145-2156 Del. HILQ587-590 Between Walker A and Cons 26 AdultCer Del. 1257-1259 Del.E291 EAA-like 27 AdultCer 2005T>C F540S Between Walker A and Cons 28 AdultCer 2358C>T R660W C-terminal to Walker B 29 AdultCer 2385C>A H667N C-terminal to Walker B 30 AMN-Cer 1146A>C T254P TM4 31 AMN 636C>T P84S TM1 32 AMN 709C>T S108L Loop1 33 AMN 1182G>A G266R Between TM4 and EAA-like 34 AMN 1197G>A E271K Between TM4 and EAA-like 35 AMN 1215G>Aa G277R Between TM4 and EAA-like 36 AMN 1255C>G S290W EAA-like 37 AMN 1581C>T R401W Between TM6 and Walker A 38 AMN 2233C>A A616D Cons 39 AMN 2385C>A H667N C-terminal to Walker B 40 Asymptomatic 2211G>A E609K Cons Amino acid residue numbers in ALDP are based on Mosser et al. [1]. Login to comment

PMID: 7494402 [PubMed] Moser HW et al: "Komrower Lecture. Adrenoleukodystrophy: natural history, treatment and outcome."

No. Sentence Comment

29 Mutation Predicted consequence Phenotype a 1 310 C -4 T R104C AMN 2 420 G -4 A A140T Cer 3 454 C -4 T R152C Cer 4 545 G -4 C R182P Addis 5 692 G -4 C Addis 693-4 del GG Frameshift at AA 231 6 770 G -4 T G277W Cer 7 1166 G -4 A R389H AMN 8 I224 G -4 A Spl mutation at AA 408 AMN 9 1389 G --+ A R464 stop AMN 10 1411 ins A Frameshift at AA 470 AMN 11 1412-3 del AA Frameshift at AA 470 Cer 12 1415-6 del AG Frameshift at AA 472 Cer 13 1415-6 del AG Frarneshift at AA 472 Cer 14 1415-6 del AG Frameshift at AA 472 Addis 15 1415-6 del AG Frameshift at AA 472 AMN 16 t415-6 del AG Frameshift at AA 472 AMN 17 1415-6 del AG Frameshift at AA 472 Cer 18 1534 G -4 A G512S Cer 19 1698 T -4 A M567K AMN 20 t817 C -4 T $604F Addis 1548 G -4 A L516L 21 1850 G -+ A R617H AMN 22 1978 G -4 A R660W AMN ~Cer=childhoodcerebralALD; Addis=Addisondisease the multiple binding sites on bovine albumin for shorter-chain fatty acids, there is only a single binding site for C26:0. Login to comment

PMID: 10190819 [PubMed] Takano H et al: "Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

42 Mutations in the ALD Gene That Result in Amino Acid Substitutions or In-frame Deletions* Patient No. Phenotype Mutation† Exon Effect of Mutation‡ Position of Mutation§ Amino Acid Identityሻ Family DataPMP70 mALDRP Pxa1p Amino Acid Deletion G4010 ACALD del.1256-1258 1 del.E291 EAA-like motif E E E CCALD G4011(s) ACALD del.2146-2157¶ 7 del.HILQ587-590 Between Walker A and B# HILE HIVQ YLLK No family history Missense Mutation G4012 CCALD A829G 1 N148S TM3 N N N AMN G1986 CCALD G984A¶ 1 D200N TM4 D D D ACALD G4013 CCALD A1026G¶ 1 N214D TM4 N N N Not available G4014 AMN G1182A 1 G266R Between TM5 and EAA motif G G Non AMN G4015(s) CCALD G1182A 1 G266R Between TM5 and EAA motif G G Non No family history G4016(s) AMN G1197A 1 E271K Between TM5 and EAA motif T E R No family history G4017(s) ACALD A1273G¶ 1 Y296C EAA motif Y Y Y No family history G4018 CCALD A1273G¶ 1 Y296C EAA motif Y Y Y Not available G4019 AMN C1587T¶ 3 R401W Between TM6 and Walker A R R R Asymptomatic carrier G4020 CCALD G1906T¶ 6 G507V Walker A# G G G Not available G4021 CCALD G1939A 6 R518Q Walker A# R R R CCALD G4022 CCALD G1939A 6 R518Q Walker A# R R R Not available G4023 ACALD T2005C¶ 6 F540S Between Walker A and B# F F F Adult asymptomatic carrier G4024(s) CCALD A2017G 6 Q544R Between Walker A and B# Q Q Q No family history G4025 CCALD C2065T 7 S560L Between Walker A and B# P P P Adult asymptomatic carrier G2469(s) ACALD C2157T¶ 7 R591W Between Walker A and B# R R R No family history G2022(s) AMN C2203T 8 S606L Between Walker A and B# S S S No family history G4026 ACALD C2364T 8 R660W C-terminal to Walker B R R R ACALD *ALD indicates adrenoleukodystrophy; ACALD, adult-onset cerebral ALD; CCALD, childhood cerebral ALD; AMN, adrenomyeloneuropathy; (s), apparently sporadic patients; and del., delete. Login to comment

PMID: 21476988 [PubMed] Zhang X et al: "Conservation of targeting but divergence in function and quality control of peroxisomal ABC transporters: an analysis using cross-kingdom expression."

No. Sentence Comment

153 Approximately 60% of X-ALD ABCD1 mutations are missense mutations, 65% of which result in no detectable ALDP, based on IF (immunofluorescence), indicating that they affect protein Table 1 Quantification of ALDP levels in X-ALD fibroblasts ALDP Mutation IF Immunoblot (% of control) p.Arg74Trp Absent 7.5 + - 0.6 p.Arg104Cys Reduced 35 + - 3.0 p.Ser149Asn Present 77 + - 3.0 p.Asp194His Present 60 + - 13.6 p.Leu220Pro Reduced 21.8 + - 5.4 p.Arg389His Present 40.6 + - 3.6 p.Arg554His Absent 1.0 + - 0.5 p.Ser606Leu Present 25 + - 1.5 p.Glu609Gly Absent 2.1 + - 1.3 p.Glu609Lys Absent 1.8 + - 0.9 p.Ala616Thr Absent 4.3 + - 1.7 p.Leu654Pro Absent 1.5 + - 1.3 p.Arg660Trp Absent 1.6 + - 0.8 p.His667Asp Absent 2.9 + - 1.0 p.Arg113fs Absent - Figure 3 Interaction of mammalian ABCD proteins with Arabidopsis Pex19 in vivo Tobacco plants stably expressing CFP-SKL were co-transfected with 35S::ABCD-YFP fusions andNLS-Pex19constructs.Leafepidermalcellswereimagedusingconfocalmicroscopy:(A-D) ALDP-YFP plus NLS-HsPex19; (E-H) ALDP-YFP plus NLS-AtPex19_1; (I-L) ALDR-YFP plus NLS-AtPex19_1. Login to comment
169 Results are means + - S.D.; n = 3. significantly in response to low temperature in ten wild-type control lines tested (see Supplementary Figure S3A at http://www.BiochemJ.org/bj/436/bj4360547add.htm); however, increased expression levels of ALDP were found in several of the X-ALD fibroblasts investigated: p.Arg74Cys, p.Arg104Cys, p.Arg554His, p.Glu609Gly, p.Ala616Thr, p.Leu654Pro and p.Arg660Trp (Figures 4A and 4B). Login to comment
172 ALDP was increased from 2-4% to ~20% of wild-type levels in cell lines bearing the mutations p.Glu609Gly, p.Ala616Thr and p.Arg660Trp, from 1 to 10% in p.Glu609Lys and p.Arg554His cells and from 45 to 75% in the p.Asp194His cell line (Figure 4A). Login to comment
173 VLCFA β-oxidation was measured in cells that were cultured at 30◦ C for 72 h, but in only one case (p.Ala616Thr) was the capacity to degrade VLCFA restored to near-control levels (Figure 4C). Login to comment
174 However, after 4 weeks of culture at 30◦ C, VLCFA levels were partially corrected in p.Arg660Trp, p.Arg554His and p.Ala616Thr fibroblasts. Login to comment
154 Approximately 60% of X-ALD ABCD1 mutations are missense mutations, 65% of which result in no detectable ALDP, based on IF (immunofluorescence), indicating that they affect protein Table 1 Quantification of ALDP levels in X-ALD fibroblasts ALDP Mutation IF Immunoblot (% of control) p.Arg74Trp Absent 7.5 + - 0.6 p.Arg104Cys Reduced 35 + - 3.0 p.Ser149Asn Present 77 + - 3.0 p.Asp194His Present 60 + - 13.6 p.Leu220Pro Reduced 21.8 + - 5.4 p.Arg389His Present 40.6 + - 3.6 p.Arg554His Absent 1.0 + - 0.5 p.Ser606Leu Present 25 + - 1.5 p.Glu609Gly Absent 2.1 + - 1.3 p.Glu609Lys Absent 1.8 + - 0.9 p.Ala616Thr Absent 4.3 + - 1.7 p.Leu654Pro Absent 1.5 + - 1.3 p.Arg660Trp Absent 1.6 + - 0.8 p.His667Asp Absent 2.9 + - 1.0 p.Arg113fs Absent - Figure 3 Interaction of mammalian ABCD proteins with Arabidopsis Pex19 in vivo Tobacco plants stably expressing CFP-SKL were co-transfected with 35S::ABCD-YFP fusions andNLS-Pex19constructs.Leafepidermalcellswereimagedusingconfocalmicroscopy:(A-D) ALDP-YFP plus NLS-HsPex19; (E-H) ALDP-YFP plus NLS-AtPex19_1; (I-L) ALDR-YFP plus NLS-AtPex19_1. Login to comment
170 Results are means + - S.D.; n = 3. significantly in response to low temperature in ten wild-type control lines tested (see Supplementary Figure S3A at http://www.BiochemJ.org/bj/436/bj4360547add.htm); however, increased expression levels of ALDP were found in several of the X-ALD fibroblasts investigated: p.Arg74Cys, p.Arg104Cys, p.Arg554His, p.Glu609Gly, p.Ala616Thr, p.Leu654Pro and p.Arg660Trp (Figures 4A and 4B). Login to comment
175 However, after 4 weeks of culture at 30e6; C, VLCFA levels were partially corrected in p.Arg660Trp, p.Arg554His and p.Ala616Thr fibroblasts. Login to comment

PMID: 7561948 [PubMed] Yasutake T et al: "Molecular analysis of X-linked adrenoleukodystrophy patients."

No. Sentence Comment

101 Patient #249 exhibited a point mutation (2364 C + T) which induced a single amino acid substitution from @'arginine to tryptophan (R660W). Login to comment
100 Patient #249 exhibited a point mutation (2364 C + T) which induced a single amino acid substitution from @'arginine to tryptophan (R660W). Login to comment

PMID: 21068741 [PubMed] Shimozawa N et al: "X-linked adrenoleukodystrophy: diagnostic and follow-up system in Japan."

No. Sentence Comment

21 Although most probands with ALD identified by us had a unique gene mutation, 6 missense mutations (p.Gly266Arg, p.Arg401Gln, p.Gly512Ser, p.Ser514Ile, p.Arg617His and p.Arg660Trp) and 1 frame-shift mutation (p.Gln472fs) were detected in two or three families (* in Figure 2). 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

255 In an early study, Yamada et al. showed that degradation of endogenous mutant ALDP (G512S and R660W) as well as wild type ALDP was suppressed by E-64 or leupeptin, which inhibit thiol proteases including lysosomal cathepsins and cytosolic calcium-activated neutral proteases in human fibroblasts (Yamada et al. 1997). Login to comment

PMID: 12175782 [PubMed] Guimaraes CP et al: "Molecular characterization of 21 X-ALD Portuguese families: identification of eight novel mutations in the ABCD1 gene."

No. Sentence Comment

66 Type of genetic alteration Exon RT-PCR fragmenta Nucleotide change Amplicon usedb /RFLP associatedc ALDP (WB) ABCD1 mRNA (NB) References Missense 1 S103R 1 F2 c.309C > G ALDe1A/þCfoI Diminished Detectable [19] 2 S108W 1 - c.323C > G ALDe1B/þRleAI Not done Not done [18] 3 S108L 1 - c.323C > T - Normal Not done [20] 4 L114P 1 F2 c.341T > C ALDe1B/ÀEcoRII Diminished Detectable Novel mutation 5 ½R236H; G512S 1 F3 [c.707G > A; ALDe1C/þNcoI Novel mutation 6 F6 c.1534G > A] ALDe6/þPstI Not detectable Not done [16,17] 6 G266R 1 F3 c.796G > A - Normal Detectable [21] 7 R518W 6 F6 c.1552C > T ALDe6/ÀHpaII Diminished Detectable [22] 8 R518Q 6 F6 c.1153G > A ALDe6/ÀBamHI Diminished Not done [23] 9 R545W 6 - c.1633A > T ALDe6/þTspRI Not done Not done Novel mutation 10 R591W 7 F7 c.1171C > T ALDe7/ÀAciI Normal Not done [24] 11 L655P 9 F8 c.1964T > C ALDe8/9/ÀSapId Diminished Detectable Novel mutation 12 R660W 9 F7/F8 c.1978C > T ALDe8/9/þBsrI Diminished Detectable [16,17,25] 13 H667L 10 F8 c.2000A > T ALDe10/þDdeId Diminished Detectable Novel mutation Nonsense 14 Q574X 7 F6 c.1720C > T ALDe7/ÀAlwNI Not detectable Detectable Novel mutation 15 W601X 8 F7 c.1802G > A ALDe8/9/ÀBsrI Not detectable Not detectable [9] Frameshift 16 fs G298 1 F3 [c.893delG; c.894C > T] ALDe1C/ÀNlaIV Not detectable Detectable Novel mutation 17, 18 fs E472 5 F5 c.1415-1416delAG - Not detectable Detectable [21,26,27] Microdeletion 19 F175del 1 F2 c.522-524delCTT d Diminished Detectable Novel mutation Splicing defect 20 Splicing IVS1 - c.900G > A - Not done Not done [10] 21 Splicing IVS7 - c.1760+1G > A - Not done Not done [18] Polymorphism 1, 5 F673F 8 F8 c.2019C > T ÀTaqI - - [28] 1, 2, 5, 11, 13 30 UTR F8 - ÀDrdI - - [27] a RT-PCR fragment (defined according to [10]) which shows heteroduplex molecules in a CSGE analysis. 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: 7825602 [PubMed] Ligtenberg MJ et al: "Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein."

No. Sentence Comment

85 The mutation T1045C created a novel HpaII site, which was confirmed Table 2 Mutations in the Putative ALD Gene in Patients Studied Genomic- Kindred Type of Mutation and Amino Acid Genomic-PCR Mutation Reference cDNA Alterationa Alterationb Exonc Primers Detectiond Phenotype' Number Missense: C696Tf ................ R104C (R) 1 303F + 821R 303F, 821R AMN 17 G832A ................ S149N (N) 1 702F + 1145R 702F, 931R AMN 8 G841C ................ R152P (K) 1 702F + 1145R 702F, 931R ChALD 27 G874Af ................ R163H (R) 1 702F + 931R 702F, 931R SympCar 14 G966C ................ D194H (D) 1 685F + 1145R 914F, 1145R ChALD 12 T1045C ................ L220P (L) 1 914F + 1145R HpaII AMN 7 G1182A ................. G266R (G) 1 702F + 1231R 914F,1231R AMN 24 G1552A ................. R389H (R) 3 1479F + 1861R 1479F,1752R AMN 20 (2X): G2211A................. E609K(E) 8 544F*+ 1078R*h 544F*, 876R* AMN 13,18 A2212G ................ E609G (E) 8 544F*+ 1078R*h 544F*, 876R* ChALD 5 C2235Tf................ R617C (R) 8 544F* + 2742R 544F*, 876R* ChALD 23 C2364Tf................ R660W (R) 9 544F* + 2742R 2312F, 1078R* AMN 21 Amino acid deletion: del 2355-2357 ........... del 1657(V) 9 849F* + 2478Rh 2312F,1078R* ChALD 6 Nonsense: C783Tf ................ Q133h 1 702F + 931R 702F, 931R ChALD 26 G797A ................ W137h 1 685F +1145R 702F,931R ChALD 10 C855T ................ Q157h 1 702F + 1145R 702F,931R AMN 9 C929A ................ Y181h 1 702F + 1145R HpaIl ChALD 15 Frameshift: delC442 ................ A19> 1 303F + 821R 303F,593R ChALD 2 del C663 ................ G92> 1 303F + 840R 576F, 821R ChALD 22 dell71-1178 ........... F261> 1 702F + 1231R 914F,1231R ChALD 28 (4X): del 1801-1802 ........... E471> 5 1781F + 1861R Polyacrylamide gel ChALD, AMN 3,4,16,25 alt 1989-2377 ........... P534> 6-9 1890F +2669R 1890F,1078R* AMN 11 Splice defect: de12021-2054 ........... R545> SA 7 1880F +2132R 1880F,2114R ChALD 1 ins 8 bp 2251f ............ R622> SA 9 849F* + 1078R*h 849F*, 1078R* AMN 19 a Nucleotide numbers refer to Mosser et al. (1993), EMBL database Z21876. Login to comment
140 Although the missense mutation R660W and the deletion of an isoleucine at position 657 are located 30 and 27 amino acids downstream of the second ATP-binding site motif, 49 respectively, they are situated within a strongly conserved region. Login to comment

PMID: 9051655 [PubMed] Yamada T et al: "Protease inhibitors suppress the degradation of mutant adrenoleukodystrophy proteins but do not correct impairment of very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts."

No. Sentence Comment

3 We investigated the stability of mutant ALDP and found from pulse-chase experiments that the respective half-lives of the normal and mutant #140 (Gly512Ser) and #249 (Arg660Trp) were 72.6, 32.1 and 26.1 min, indicative that mutant ALDPs are less stable than normal ones. Login to comment
19 Two, #240 and #249, respectively had the missense mutations Gly512Ser (G1920A) and Arg660Trp (C2364T). Login to comment
37 Normal and mutant (Gly512Ser or Arg660Trp) ALDP cDNAs synthesized by reverse-transcription and PCR were inserted into the expression vector, pCAGGS (8). Login to comment
82 Gly512Ser and Arg660Trp mutations in their patients resulted in a complete lack of immunoreactivity, as they did in our patients (2). Login to comment

PMID: 7581394 [PubMed] Kok F et al: "Mutational analysis of patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

131 3' deletion 3' deletion 3' deletion 3' deletion R104C A141T R152C R182P Frameshift at AA 231 G277W R389H Spl mutation at AA 408 Q466 stop Frameshift at AA 470 Frameshift at AA 470 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 G512S M566K S606L L516L R617H R660W - - Exons 3-10 Exons 7-10 Exons 8-10 Exons 7-10 33 Anglos 5 Scott 8 Anglos 7 Anglos 11 Jewish 36 Irish 51 Italian 37 Filipino 28 Anglos 23 Anglos 11 Anglos 8 Anglos 40 Italian 22 German 4 Anglos 5 black 8 Anglos 31 Anglos 10 Anglos 28 Anglos 22 Italian 8 German 35 German 7 Hispanic 28 German 24 Anglos 18 Jewish 9 Hispanic AMNa C E R ~ Cer Add' Cer AMN AMN AMN AMN Cer Cer Cer Add AMN AMN Cer Cer Cer AMN Add AMN AMN Cer AMN Cer AMN AMN AMN 5 Cer,AMN,Add 4 Cer,AMN 1 Cer 5 Cer,AMN,Add 1 4 2 1 2 2 5 Adopted 5 2 15 1 13 2 2 1 Cer AMN AMN,Add AMN Cer,AMN Cer,AMN Cer,AMN,Add ? Login to comment

PMID: 17202797 [PubMed] Takahashi N et al: "[Adrenoleukodystrophy: structure and function of ALDP, and intracellular behavior of mutant ALDP with naturally occurring missense mutations]."

No. Sentence Comment

49 変異型 ALDP の分解過程の解析新生タンパク質が正しいフォールディングを受けることは,そのタンパク質の正常な機能発現のために必須である．遺伝子変異などが存在すると,タンパク質がミスフォールディングされる．このミスフォールドタンパクが細胞外へ分泌されたり,細胞内に蓄積したりすると生体にとって極めて有害になるため,このようなタンパクはプロテアソーム,リソソーム等によって迅速に分解される．ちなみに,嚢胞性線維症の原因タンパク質 CFTR は細胞膜イオンチャネルとして機能する ABC タンパク質であるが,変異 CFTR は小胞体膜からプロテアソームにリクルートされ分解されることが報告されている．32,33) しかしながら,変異型 ALDP を始めとして,ペルオキシソーム膜タンパク質についての解析はほとんど行われていない．変異型 ALDP の一過性発現と安定過剰発現実験より,ALDP(S606L, R617H, H667D, R104C)は, プロテアーゼにより分解されていると推定された．そこで,ALDP-GFP(H667D)を発現している CHO 細胞に各種プロテアーゼ阻害剤を処理し,解析を行った．その結果,プロテアソーム阻害剤である lactacystin を処理した細胞では ALDP-GFP 及び ALDP のバンドが出現した ( Fig. 4 )．一方 , leupeptin, AEBSF, E64d には効果がなかった．また他のプロテアソーム阻害剤である MG132 も有効であった．さらにプロテアソーム阻害剤により分解を逃れた変異型 ALDP-GFP(H667D)の細胞内局在を蛍光抗体法で観察すると,ペルオキシソームに局在していることが確認された．一方,変異型 ALDP(R104C)のフラグメント化は上記プロテアーゼ処理では阻害されなかった．さらに ALD 患者由来細胞の内因性変異 ALDP の分解とプロテアソーム分解系の関与について確認するため,変異型 ALDP(R617H)を持つ患者由来線維芽細胞を用いてタンパク分解の阻害実験を行った．その結果,lactacystin と MG132 処理により, ALDP のバンドが出現した．以上の結果より,ペルオキシソーム膜上にはミスフォールドしたタンパク質を認識する仕組みが存在し,プロテアソーム及び他のプロテアーゼを介して排除していることが示唆された．一方,山田らは ALD 患者線維芽細胞を［35 S］メチオニンでパルスチェイスすることにより,変異型 ALDP(G512S, R660W)の分解が E-64 と leupepu- tin により抑制されることを報告している．34) 彼らの実験ではプロテアソーム阻害剤については実験していないので,プロテアソームの関与は不明であるが,変異型 ALDP の分解には,複数のプロテアーゼが関与している可能性がある． 7. Login to comment
46 ᜕ᶒɂb; ALDP Ĳe;ᑖYe3;Έe;a0b;Ĳe;Ye3;᪆ Ab0;˯f;bf;f3;d1;af;cea;İc;b63;௱௤d5;a9;fc;eb;c7;a3;f3;b0;ఔ5d7;௫ Ĵb;௭௼Ĳf;,ıd;Ĳe;bf;f3;d1;af;cea;Ĳe;b63;e38;Ĳa;a5f;Pfd;˿a;Ife;Ĳe;ıf;ఉ Ĳb;fc5;♐௻௢Ĵb;&#ff0e;΋a;f1d;b50;᜕ᶒĲa;௽İc;b58;ᙠ௳Ĵb;௼,bf;f3; d1;af;cea;İc;df;b9;d5;a9;fc;eb;c7;a3;f3;b0;௯Ĵc;Ĵb;&#ff0e;௭Ĳe;df;b9;d5; a9;fc;eb;c9;bf;f3;d1;af;İc;d30;Pde;᜜ఆᑖccc;௯Ĵc;ıf;Ĵa;,d30;Pde;ᑁ Ĳb;Tc4;a4d;௱ıf;Ĵa;௳Ĵb;௼˯f;f53;Ĳb;௼௷௺ᬿఉ௺ᨵbb3;Ĳb;Ĳa;Ĵb; ıf;ఉ,௭Ĳe;ఐ௦Ĳa;bf;f3;d1;af;Ĳf;d7;ed;c6;a2;bd;fc;e0;,ea;bd; bd;fc;e0;b49;Ĳb;ఐ௷௺fc5;΅f;Ĳb;ᑖYe3;௯Ĵc;Ĵb;&#ff0e;௵Ĳa;ĳf;Ĳb;,8a2; Pde;ឋdda;dad;Kc7;Ĳe;țf;8e0;bf;f3;d1;af;cea; CFTR Ĳf;d30;Pde;̳c;a4;aa; f3;c1;e3;cd;eb;௼௱௺a5f;Pfd;௳Ĵb; ABC bf;f3;d1;af;cea;௻௢Ĵb; İc;,᜕ᶒ CFTR Ĳf;c0f;Pde;f53;̳c;İb;఑d7;ed;c6;a2;bd;fc;e0;Ĳb; ea;af;eb;fc;c8;௯Ĵc;ᑖYe3;௯Ĵc;Ĵb;௭௼İc;ᛇȠa;௯Ĵc;௺௤ Ĵb;&#ff0e; 32,33) ௱İb;௱Ĳa;İc;఑,᜕ᶒɂb; ALDP ఔ;cb;ఉ௼௱ ௺,da;eb;aa;ad;b7;bd;fc;e0;̳c;bf;f3;d1;af;cea;Ĳb;௸௤௺Ĳe;Ye3;᪆ Ĳf;ĳb;௼క௽ʹc;Ĵf;Ĵc;௺௤Ĳa;௤&#ff0e; ᜕ᶒɂb; ALDP Ĳe;e00;Έe;ឋ˿a;Ife;௼b89;b9a;Έe;ᒖ˿a;Ife;b9f; a13; ఐĴa;,ALDP (S606L, R617H, H667D, R104C) Ĳf;, d7;ed;c6;a2;fc;bc;Ĳb;ఐĴa;ᑖYe3;௯Ĵc;௺௤Ĵb;௼?a8;b9a;௯Ĵc;ıf;&#ff0e; ıd;௭௻,ALDP-GFP(H667D)ఔ˿a;Ife;௱௺௤Ĵb; CHO d30;Pde;Ĳb;ᔜa2e;d7;ed;c6;a2;fc;bc;σb;bb3;ᒐఔ3e6;ᳮ௱,Ye3; ᪆ఔʹc;௷ıf;&#ff0e;ıd;Ĳe;d50;ʧc;,d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐ௻௢ Ĵb; lactacystin ఔ3e6;ᳮ௱ıf;d30;Pde;௻Ĳf; ALDP-GFP 5ca;ఁ ALDP Ĳe; d0; f3; c9; İc; 3fa; Ife; ௱ ıf; ( Fig. 4 ) &#ff0e; e00; Ab9; , leupeptin, AEBSF, E64d Ĳb;Ĳf;4b9;ʧc;İc;Ĳa;İb;௷ıf;&#ff0e;ĳe; ıf;ed6;Ĳe;d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐ௻௢Ĵb; MG132 ఊᨵ4b9; ௻௢௷ıf;&#ff0e;௯఑Ĳb;d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐĲb;ఐĴa;ᑖYe3; ఔ⌫Ĵc;ıf;᜕ᶒɂb; ALDP-GFP(H667D)Ĳe;d30;Pde;ᑁc40; ᙠఔVcd;ᐝᢙf53;cd5;௻Yb3;bdf;௳Ĵb;௼,da;eb;aa;ad;b7;bd;fc;e0;Ĳb; c40;ᙠ௱௺௤Ĵb;௭௼İc;Nba;a8d;௯Ĵc;ıf;&#ff0e;e00;Ab9;,᜕ᶒɂb; ALDP (R104C) Ĳe;d5;e9;b0;e1;f3;c8;ᓄĲf;e0a;a18;d7;ed;c6;a2;fc; bc;3e6;ᳮ௻Ĳf;σb;bb3;௯Ĵc;Ĳa;İb;௷ıf;&#ff0e; ௯఑Ĳb; ALD <a3;ὅᵫᩭd30;Pde;Ĳe;ᑁ8e0;ឋ᜕ᶒ ALDP Ĳe;ᑖYe3;௼d7;ed;c6;a2;bd;fc;e0;ᑖYe3;cfb;Ĳe;_a2;e0e;Ĳb;௸௤௺Nba;a8d; ௳Ĵb;ıf;ఉ,᜕ᶒɂb; ALDP(R617H)ఔᢝ௸<a3;ὅᵫ ᩭdda;dad;Rbd;d30;Pde;ఔᵨ௤௺bf;f3;d1;af;ᑖYe3;Ĳe;σb;bb3;b9f; a13;ఔʹc; ௷ıf;&#ff0e;ıd;Ĳe;d50;ʧc;,lactacystin ௼ MG132 3e6;ᳮĲb;ఐĴa;, ALDP Ĳe;d0;f3;c9;İc;3fa;Ife;௱ıf;&#ff0e;ee5;e0a;Ĳe;d50;ʧc;ఐĴa;,da; eb;aa;ad;b7;bd;fc;e0;̳c;e0a;Ĳb;Ĳf;df;b9;d5;a9;fc;eb;c9;௱ıf;bf;f3;d1; af;cea;ఔa8d;b58;௳Ĵb;ed5;d44;ĳf;İc;b58;ᙠ௱,d7;ed;c6;a2;bd;fc;e0;5ca; ఁed6;Ĳe;d7;ed;c6;a2;fc;bc;ఔecb;௱௺᣸◀௱௺௤Ĵb;௭௼İc;̙a; ᖂ௯Ĵc;ıf;&#ff0e; e00;Ab9;,c71;ᵪ఑Ĳf; ALD <a3;ὅdda;dad;Rbd;d30;Pde;ఔ &#ff3b;35 S&#ff3d; e1;c1; aa;cb;f3;௻d1;eb;b9;c1;a7;a4;b9;௳Ĵb;௭௼Ĳb;ఐĴa;,᜕ᶒɂb; ALDP (G512S, R660W) Ĳe;ᑖYe3;İc; E-64 ௼ leupepu- tin Ĳb;ఐĴa;ᢓᑴ௯Ĵc;Ĵb;௭௼ఔᛇȠa;௱௺௤Ĵb;&#ff0e; 34) f7c;఑ Ĳe;b9f; a13;௻Ĳf;d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐĲb;௸௤௺Ĳf;b9f; a13;௱ ௺௤Ĳa;௤Ĳe;௻,d7;ed;c6;a2;bd;fc;e0;Ĳe;_a2;e0e;Ĳf;e0d;ʔe;௻௢Ĵb; İc;,᜕ᶒɂb; ALDP Ĳe;ᑖYe3;Ĳb;Ĳf;,⋋ᦪĲe;d7;ed;c6;a2;fc; bc;İc;_a2;e0e;௱௺௤Ĵb;5ef;Pfd;ឋİc;௢Ĵb;&#ff0e; 7. Login to comment

PMID: 20799350 [PubMed] Kelly L et al: "Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains."

No. Sentence Comment

50 Disease-associated nsSNPs at Three Structural Hotspots in Human ABC Transporter NBDs Gene Disease Position ARA motif ABCB11 BRIC2 A570T ABCD1 X-ALD A616V CFTR CF A559T ABCC6 PXE R765Q ABCC8 HHF1 R841G ABCC8 HHF1 R1493Q ABCC8 HHF1 R1493W ABCD1 X-ALD R617C ABCD1 X-ALD R617G ABCD1 X-ALD R617H CFTR CF R560K CFTR CF R560S CFTR CF R560T ABCA1 HDLD1 A1046D ABCB4 ICP A546D C-loop 1 motif ABCC8 HHF1 D1471H ABCC8 HHF1 D1471N CFTR CBAVD G544V ABCC8 HHF1 G1478R C-loop2 motif ABCA4 STGD1 H2128R ABCC8 HHF1 K889T ABCD1 X-ALD R660P ABCD1 X-ALD R660W ABCA1 HDLD2 M1091T ABCA4 STGD1 E2131K ABCA12 LI2 E1539K ABCA4 STGD1 and CORD3 E1122K CFTR CF L610S ABCC8 HHF1 L1543P ABCA1 Colorectal cancer sample; somatic mutation A2109T ABCC9 CMD1O A1513T ABCD1 X-ALD H667D CFTR CF A613T ABCA1 HDLD2 D1099Y ABCD1 X-ALD T668I CFTR CF D614G ABCA4 STGD1 R2139W ABCA4 STGD1 R1129C ABCA4 ARMD2, STGD1, and FFM R1129L Disease abbreviations are as follows: BRIC2, benign recurrent intrahepatic cholestasis type 2; X-ALD, X-linked adrenoleukodystrophy; CF, cystic fibrosis; PXE, Pseudoxanthoma elasticum; HHF1, familial hyperinsulinemic hypoglycemia-1; HDLD1, high density lipoprotein deficiency type 1; ICP, intrahepatic cholestasis of pregnancy; CBAVD, congenital bilateral absence of the vas deferens; STGD1, Stargardt disease type 1; HDLD2, high density lipoprotein deficiency type 2; LI2, ichthyosis lamellar type 2; CORD3, cone-rod dystrophy type 3; CMD1O, cardiomyopathy dilated type 1O; ARMD2, age-related macular degeneration type 2; FFM, fundus flavimaculatus. Login to comment

PMID: 23835273 [PubMed] Hung KL et al: "Mutational analyses on X-linked adrenoleukodystrophy reveal a novel cryptic splicing and three missense mutations in the ABCD1 gene."

No. Sentence Comment

5 In addition, three previously described missense mutations (c.965T>C, c.1978C>T, and c.2006A>G), leading to aberrant ABCD1 of p.Leu322Pro, p.Arg660Trp, and p.His669Arg, were also identified in Malaysian probands. Login to comment
75 The mutation caused the conversion of a codon for arginine at position 660 to one encoding for a tryptophan (p.Arg660Trp) in ABCD1.21-23 Both the ALD-4 proband and his mother carried the A-toG transition mutation (c.2006A>G) in exon 10 of the ABCD1 gene based on genomic DNA typing results (Fig 3). Login to comment
98 Three missense mutations (c.965T>C, c.1978C>T, and c.2006A>G), leading to aberrant ABCD1 of p.Leu322Pro, p.Arg660Trp, and p.His669Arg, were also identified in Malaysian probands with X-ALD of the childhood cerebral form, adolescent cerebral phenotype, and adrenomyeloneuropathy with cerebral involvement, respectively. Login to comment
99 All three missense mutations have been reported to reoccur in three or more X-ALD kindred around the world.19-22,24 All three affected amino acids were highly conserved in ABCD1 among different species or among other peroxisomal ABC transporter homologues, suggesting their possible important role in maintaining proper ABCD1 structure or function.25-27 The replacement of leucine at position 322, localized to the fifth transmembrane domain of ABCD1, with proline is most likely to disrupt membrane spanning a-helical conformation because of the relatively high differences in free-energy change (DDG0 ) for proline to adapt a-helical conformation, as compared with that for alanine.28 On the other hand, both p.Arg660Trp and p.His669Arg, localized to the cytoplasmic domain of ABCD1, have been reported to affect protein stability, resulting in dramatic reduction (<3% in normal) in the amount of ABCD1 based on either immunofluorescence or immunoblotting.22,23,29 It is interesting to note that a cluster of stability affecting mutations involving the region between Pro654 and His669 near the carboxyl terminus of ABCD1 has no known structural or functional significance,22,23,30,31 suggesting their possible roles in cellular sensing or turnover of mutant proteins. Login to comment
113 In addition, three missense mutations (c.965T>C, c.1978C>T, and c.2006A>G), leading to aberrant ABCD1 of p.Leu322Pro, p.Arg660Trp, and p.His669Arg, were also identified in Malaysian X-ALD kindred. A polymorphism in intron 9 (c.1992-32c/t; refSNP: rs4898368) of the ABCD1 gene was also commonly observed in both Taiwanese and Malaysian populations. Login to comment

PMID: 24480483 [PubMed] Engelen M et al: "X-linked adrenoleukodystrophy in women: a cross-sectional cohort study."

No. Sentence Comment

141 Table 1 Summary of symptoms and signs of all the female participating in the study Family Age (years) Urinary incontinence Faecal incontinence Gait disorder Sensory complaints Sensory disturbance Spasticity Weakness Pathological reflexes EDSS Mutation ABCD1 protein A 44 No No Yes No No No No Yes 1.0 p.Pro480Thr Absent A 56 Yes Yes No No No No No Yes 1.5 p.Pro480Thr Absent AA 45 No No No No No No No No 0 p.Arg660Trp Absent AA 59 Yes No Yes No No No Yes Yes 3.5 p.Arg660Trp Absent AA 75 Yes No Yes No Yes Yes Yes Yes 6.0 p.Arg660Trp Absent B 42 Yes Yes Yes No Yes Yes Yes Yes 4.0 p.Leu220Pro Reduced B 44 No No No No No No No No 0 p.Leu220Pro Reduced B 44 No No No No No No No No 0 p.Leu220Pro Reduced B 51 No No No Yes Yes No No No 1.0 p.Leu220Pro Reduced B 59 No No No Yes Yes No Yes No 2.0 p.Leu220Pro Reduced C 44 No No No No No No No No 0 p.Gln133* Absent D 38 Yes Yes Yes No Yes Yes Yes Yes 6.0 p.Leu654Pro Absent D 57 Yes No Yes Yes Yes No No Yes 5.5 p.Leu654Pro Absent E 31 No No No No No No No No 0 p.Arg74Trp Absent E 37 No No No No No No No No 0 p.Arg74Trp Absent E 60 No No Yes No Yes Yes Yes Yes 5.5 p.Arg74Trp Absent F 35 No No No No No No No No 0 p.Met1Val Absent G 42 No Yes No No No No No No 1.0 p.Ala245Asp Present H 61 Yes Yes Yes Yes Yes No No Yes 3.5 exon8-10del Absent I 71 No No No No Yes No No Yes 2.0 p.Glu609Lys Absent J 42 No No No No Yes No No Yes 1.5 p.Glu90* Absent K 31 No No No No No No No No 0 p.Pro543Leu Absent K 48 Yes No No No Yes No No Yes 2.5 p.Pro543Leu Absent K 57 No No Yes Yes Yes No Yes Yes 3.5 p.Pro543Leu Absent K 60 Yes No No No Yes No No Yes 3.5 p.Pro543Leu Absent L 51 Yes No Yes No Yes Yes Yes Yes 6.5 p.Ile657del Absent M 22 No No No No No No No No 0 p.Ser149Asn Reduced M 40 No No No No No No No No 0 p.Ser149Asn Reduced N 29 No No No No No No No No 0 p.Arg389His Reduced N 45 Yes No No Yes No No No No 2.0 p.Arg389His Reduced N 57 Yes Yes Yes Yes Yes No No No 3.5 p.Arg389His Reduced N 70 No No Yes No Yes No Yes Yes 3.5 p.Arg389His Reduced O 40 Yes Yes Yes Yes Yes No No Yes 3.5 p.Glu609Lys Absent P 59 Yes Yes Yes Yes Yes Yes Yes Yes 6.0 p.Leu215* Absent Q 39 No Yes Yes No Yes No No No 3.0 p.Val208Trpfs Absent R 28 No No No No No No No No 0 p.Pro480Thr Absent S 35 No No No No No No No No 0 p.His283Tyr Reduced (continued) Correlation studies of X-inactivation with asymptomatic or symptomatic status The distribution of ABCD1 allele-specific expression (which will be referred to as the pattern of X-inactivation) is shown in Fig. 5A. Login to comment