ABCMdb

ABCD1 p.Arg554His

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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

164 X-ALD Mutations Identified in the ABCD1 Gene Allele Exon Mutation Protein Remark fs P42 1 125insC n.d. # fs P84 1 253insC n.d. # E90K 1 268G>A n.d. # S98L 1 293C>T Present S98L 1 293C>T Present R104H 1 311G>A n.d. fs A112 1 337delC Absent # R113C 1 337C>T Present # R113P 1 338G>C n.d. # Q133X 1 397C>T Absent W137X 1 411G>A Absent P143S 1 427C>T n.d. S149N 1 446G>A Present R152S 1 454C>A n.d. R152C 1 454C>T Present R152L 1 455G>T Reduced # S161P 1 481T>C n.d. # R163P 1 488G>C n.d. Y174C 1 521A>G Absent Y174C 1 521A>G n.d. Q177X 1 529C>T Absent Y181C 1 542A>G n.d. fs Y181 1 544ins8bp n.d. # Q195X 1 583C>T n.d. # T198K 1 593C>A n.d. # fs S207 1 621del664bp Absent # SV207-8insAAS 1 622-23ins9bp n.d. # K217E 1 649A>G Present # P218T 1 652C>A n.d. V224E 1 671T>G n.d. # L229P 1 686T>C n.d. L229P 1 686T>C n.d. fs S235 1 706delCGTG n.d. # W242X 1 726G>A Absent G266R 1 796G>A n.d. G266R 1 796G>A n.d. R274W, R280C 1 820C>T, 838C>T n.d. # R285P 1 854G>C n.d. S290X 1 869C>A Absent # E291del 1 871-73delGAG Absent Y296C 1 887A>G n.d. Y296C 1 887A>G n.d. fs E300 IVS1 IVS1+1g>t n.d. # fs E300 IVS1 IVS1-1g>a n.d. # S315X 2 944C>A n.d. # K336M 2 1007A>T n.d. # G343D 2 1028G>A n.d. # R401Q 3 1202G>A Present R401Q 3 1202G>A Present K407X 3 1219A>T n.d. # E427del 4 1279-81delGAA n.d. # Q430X 4 1288C>T n.d. # R464X 4 1390C>T n.d. fs E471 5 1415delAG Absent fs E471 5 1415delAG Absent fs E471 5 1415delAG Absent fs E471 5 1415delAG Absent C511X 6 1533C>A n.d. # R518Q 6 1553G>A Absent fs G528 6 1586-90del Absent # fs Y532 6 1599delG Absent # P543L 6 1628C>T Absent P543L 6 1628C>T Absent fs Q544 6 1628-34duplicated n.d. # fs R545 IVS 6 IVS6+1g>c n.d. # R554H 7 1661G>A Absent fs Q556 7 1670delTG n.d. # (continued) replaced by a pyrimidine (C or T) or vice versa, and transitions, comprising the substitution of one purine by the other, or of one pyrimidine by the other. Login to comment

PMID: 15811009 [PubMed] Coll MJ et al: "X-linked adrenoleukodystrophy in Spain. Identification of 26 novel mutations in the ABCD1 gene in 80 patients. Improvement of genetic counseling in 162 relative females."

No. Sentence Comment

6 Only six mutations (Y174S, G277R, FsE471, R518Q, P543L, and R554H) were found in more than one family. Login to comment
7 Mutations G277R, P543L, and R554H were the most frequent, each of them being found in three patients (5%). Login to comment
67 With respect to the 12 missense mutations (R17H, V102E, R120P, N148Y, G277R, L279P, A396T, M501L, K533E, D561V, R617L, and S656F), only in four cases (L279P, K533E, R554H, and S656F mutations), three of which (K533E, R554H, and S656F) affect adenosine triphosphate-binding domain or boundaries, could negative ALDP protein expression be established. Login to comment
72 Only six mutations (Y174S, G277R, FsE471, R518Q, P543L, and R554H) have been found repeated in patients belonging to different families. Login to comment
74 In contrast, mutations G277R, P543L, and R554H are the most frequent in the Spanish population, each one accounting for three independent patients (5%) with different phenotypes, as occurs in other populations (for more information: http://www.x-ald.nl). 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: 9242200 [PubMed] Korenke GC et al: "Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings."

No. Sentence Comment

120 Sixteen of these mutations have been published before (11, 21); the remaining 12 mutations comprise nine missense mutations (A141T, Y281H, R389H, G512S, P543L, R554H, Y559H, R617H, R679R), two frame-shift mutations (del 740, del 2132) and one splice site mutation (ins 8 bp 2252). Login to comment

PMID: 15643618 [PubMed] Montagna G et al: "Identification of seven novel mutations in ABCD1 by a DHPLC-based assay in Italian patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

95 Summary of Mutations in ABCD1 (RefSeq: NM_000033.2) Identified in this Study ABCD1 gene cDNA level Protein level Exon 1 c.145_146ins4 p.Pro49fs Exon 1 c.264C>G p.Cys88Trp Exon 1 c. 454C>T p.Arg152Cys Exon 1 c.542A>G p.Tyr181Cys Exon 2 c.919C>T p.Gln307X Exon 2 c.994C>T p.Gln332X Exon 2 c.1027G>A p.Gly343Ser Exon 5 c.1415_1416del2 p.Glu471fs Exon 6 c.1508T>C p.Leu503Pro Exon 6 c.1540A>C p.Ser514Arg Exon 7 c.1661G>A p.Arg554His Novel variants are in bold. Login to comment

PMID: 15800013 [PubMed] Asheuer M et al: "Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy."

No. Sentence Comment

76 Mutation Amino acid alteration Type of mutation at the protein level Tissue sample CCER1 521A.G Y174C Missense CCER2 1414insC fsE471 Frame shift CCER3 Unknown Unknown Unknown Fibroblast CCER4 411G.A W137X Nonsense CCER5 1961T.C L654P Missense CCER6 529C.T Q177X Nonsense CCER7 901-1G.A fsE300 Frame shift CCER8 796G.A G266R Missense CCER9 1822G.A G608S Missense Brain CCER10 1390C.A R464X Nonsense CCER11 253-254insC fsP84 Frame shift CCER12 619_627del S207_A209del Deletion AMN-C1 1414-1415insC fsE471 Frame shift AMN-C2 1661G.A R554H Missense AMN-C3 1585delG fsG528 Frame shift Fibroblast AMN-C4 1661G.A R554H Missense AMN-C5 1825G.A E609K Missense AMN-C6 919C.T Q307X Nonsense AMN-C7 1850G.A R617H Missense AMN-C8 887A.G Y296C Missense AMN-C9 965T.C L322P Missense Brain AMN-C10 1390C.T R464X Nonsense AMN-C11 [1165C.T;1224 þ 1GT.TG] [R389C;fSE408] Missense; frame shift AMN-C12 1661G.A R554H Missense AMN-C13 [1997A.C;2007C.G] [Y666S;H669Q] Missense AMN-C14 1755delG fsH586 Frame shift AMN1 529C.T Q177X Nonsense AMN2 1999C.G H667D Missense AMN3 1415delAG fsE471 Frame shift Fibroblast AMN4 337delC fsA112 Frame shift AMN5 310C.T R104C Missense AMN6 919C.T Q307X Nonsense AMN7 323C.T S108L Missense Brain All mutation designations conform to the nomenclature described by Antonarakis and den Dunnen (30,31). Login to comment

PMID: 22176151 [PubMed] Engelen M et al: "X-linked adrenomyeloneuropathy due to a novel missense mutation in the ABCD1 start codon presenting as demyelinating neuropathy."

No. Sentence Comment

29 Lanes 1 and 4, protein extracts from two different control subjects; lane 2, the index patient; lane 3, protein extract from an X-ALD patient with a p.Arg554His mutation that results in no detectable ALDP (www.x-ald.nl). Login to comment

PMID: 22479560 [PubMed] Pereira Fdos S et al: "Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

24 Family/Index case Phenotype at diagnosis Mutation Exon/IVS Mutation type Effect on protein (cDNA) Effect on protein (mRNA) Protein localization Origin of mutations Origin of family 1/Female asymptomatic p.Gly512Ser (Feigenbaum V et al. 1996) E6 Missense c.1534G.A GGC.AGC NBF de novo Southern Brazil 2/Female asymptomatic p.Ser606Leu (Fanen P et al., 1994) E8 Missense c.1817C.T UCG.UUG NBF Inherited Southern Brazil 3/Male AMN p.Trp601X (Gartner J et al.,1998) E8 Stop codon c.1802C.A Truncated NBF Inherited Southern Brazil 4/Female asymptomatic p.Arg617His (Fanen P et al., 1994) E8 Missense c.1850G.A CGC.CAC NBF ND Southern Brazil 5/Male AMN p.Pro623Leu # E9 Missense c.1868C.T CCC.CUC NBF Inherited Southern Brazil 6/Male AO p.Trp326X (Barcelo A et al, 1996) E2 Stop codon c.978G.A Truncated TMD Inherited Southern Brazil 8/Female asymptomatic p.Glu577X # E7 Stop codon c.1729G.T Truncated NBF Inherited Southern Brazil 9/Male asymptomatic p.Arg554His (Smith KD et al., 1999) E7 Missense c.1661G.A CGU.CAU NBF Inherited Southern Brazil 10/Male CALD p.Arg518Gln (Imamura A et al., 1997) E6 Missense c.1553G.A CGG.CAG NBF Inherited Southern Brazil 11/Male AO p.Tyr33_Pro34fsX34 # E1A Frameshift+stop codon c.99_102delC Truncated - Inherited Southern Brazil 12/Female asymptomatic p.Gly266Arg (Fuchs S et al., 1994) E7 Missense c.1653insG Truncated TMD ND Southern Brazil 20/Male CALD p.Arg538fs # E6 Frameshift c.1614_1615dup27 Elonged NBF de novo Southern Brazil 21/Male CALD p.Ala232fsX64 # E2 Frameshift+stop codon c.696_697del11 Truncated TMD Inherited Southern Brazil 22/Male CALD p.Trp137fsX57 # E1B Frameshift+stop codon c.411_412insC Truncated TMD Inherited Northern Brazil 23/Male asymptomatic p.Trp679X (Waterham HR et al, 1998) E10 Stop codon c.2037G.A Truncated NBF ND Southern Brazil 24/Male AO p.Tyr296Cys (Takano H et al., 1999) E2 Missense c.887A.G UAU.UGU TMD Inherited Southern Brazil 27/Male CALD p.Leu628Glu # E9 Missense c.1883T.A CUG.GAG NBF Inherited Southern Brazil 29/Male CALD p.Pro546fsX? 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

PMID: 23664929 [PubMed] Zhan ZX et al: "Exome sequencing released a case of X-linked adrenoleukodystrophy mimicking recessive hereditary spastic paraplegia."

No. Sentence Comment

3 A missense mutation (c.1661G>A, p.R554H) was identified in ABCD1. Login to comment
77 Open symbols &#bc; unaffected; filled symbols &#bc; affected; symbols with a diagonal line &#bc; deceased subjects; symbols with a point &#bc; carrier; squares &#bc; male; circles &#bc; female; arrow &#bc; the proband; minus &#bc; the wild-type allele; plus &#bc; the mutation allele, c.1661G>A, p.R554H in exon 7 of ABCD1. Login to comment
100 Finally, ABCD1, the causative gene for X-ALD, which contained a mutation of c.1661G>A, p.R554H in exon 7, was suggested to be the causative gene of the family. Login to comment
115 Subsequently, WES uncovered the mutation c.1661G>A, p.R554H in ABCD1 in both sibs. Login to comment

PMID: 24719134 [PubMed] Park HJ et al: "Clinical and genetic aspects in twelve Korean patients with adrenomyeloneuropathy."

No. Sentence Comment

89 The Mutational Analysis of Korean Patients with Adrenomyeloneuropathy Exon Mutation Allele Type Reference Adrenomyeloneuropathy without cerebral involvement 1 1 c.479T>C p.Leu160Pro Missense Sutovsk&#fd;, et al.13 2 3 c.1166G>A p.Arg389His Missense Kok, et al.14 3 9 c.1970_72del p.Ile657del In-frame deletion Ligtenberg, et al.15 4 1 c.421G>A p.Ala141Thr Missense Kok, et al.14 5 Not found 6 7 c.1679C>T p.Pro560Leu Missense Kemp, et al.6 7 Not available Adrenomyeloneuropathy with cerebral involvement 8 7 c.1679C>T p.Pro560Leu Missense Kemp, et al.6 9 1 c.225_242del p.Trp77_Leu82del Deletion Lee, et al.9 Spinocerebellar phenotype 10 1 c.277_296dup20 p.Leu93fs Frameshift Novel 11 7 c.1661G>A p.Arg554His Missense Kemp, et al.6 12 IVS1 c.901-1G>A p.Val301fs Frameshift Kemp, et al.6 IVS, intervening sequence. Login to comment

PMID: 26260157 [PubMed] Jiang MY et al: "Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China."

No. Sentence Comment

74 Reference range Table 1 ABCD1 mutations and phenotypes of 19 X-linked adrenoleukodystrophy male patients Patient Exon Nucleotide change Amino acid change Phenotype 1 1 c.102_103insCa p.Leu35LeufsX159a AO 2 1 c.347_348delGAinsATa p.Gly116Aspa CCALD 3 1 c.521A>G p.Tyr174Cys CCALD 4 1 c.785C>Aa p.Ser262Xa CCALD 5 2 c.982G>Ta p.Val328Phea AO 6 3 c.1109 T>Aa p.Leu370xa CCALD 7 3 c.1180delGab p.Ala394ArgfsX15a CCALD 8 3 c.1180delGab p.Ala394ArgfsX15a CCALD 9 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 10 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 11 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 12 5 c.1415_16delAG p.Gln472Argfs*83 AO 13 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 14 6 c.1553G>A; c.1548G>A p.Arg518Gln; p.Leu516Leu CCALD 15 7 c.1661G>A p.Arg554His CCALD 16 7 c.1724_1725insCa p.Leu576ProfsX24a AO 17 9 c.1894A>C p.Thr632Pro CCALD 18 - IVS2_IVS5del - CCALD 19 - IVS2_IVS5del - AO a Novel mutation b De novo mutation have been identified in the ABCD1 gene, in which 695 (44 %) mutations appear to be non-recurrent. Login to comment