ABCMdb

ABCD1 p.His669Arg

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Publications

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6 In one patient 2 changes were found: a known missense (p.His669Arg) and an unpublished amino acid substitution (p.Ala19Ser). Login to comment
66 AMN 2 Phenotype 1 cDNA mutation Protein level Exon/Intron Polymorphisms Exon/Intron Protein level 1 AMN c.2006A.G p.His669Arg 10 c.55G.T 1 p.Ala19Ser c.1992-32C.T 9 2 CCALD c.1137dupC p.Glu380Argfs*21 3 c.1992-32C.T 9 c.2019C.T 10 p.Phe673Phe 3 AO c.1022C.A p.Ala341Asp 2 c.1634+14T.A 6 c.1992-32C.T 9 4 AO c.1081+5G.C Splice mutation c.1548G.A 6 p.Leu516Leu r.907_1494del p.Leu303_Glu498 IVS2 c.1992-32C.T 9 5 Asymptomatic c.1640A.G p.Tyr547Cys 7 6 CCALD c.1714_1725dek12bp p.Ser572_Asp575del 7 7 Adolescent cerebral ALD c.761delC p.Thr254Argfs*82 1 c.1634+14T.A 6 8 -- c.1259A.C p.His420Pro 1 9 AMN c.2006A.G p.His669Arg 10 c.1992-32C.T 9 10 CCALD c.852_853insACTC p.Ser284fs*16 1 1 Nucleotides numbered reflects cDNA numbering with +1 corresponding to the A of the ATG initiation codon in the reference sequence (NM000033), according to journal guidelines (www.hgvs.org/mutnomen). Login to comment
87 We identified nine different mutations: one missense mutation was previously described (p.His669Arg) and eight were new ones (Table 1). Login to comment
114 In patient 1 (Table 1), we identified two different substitutions, one in exon 1 and other in exon 10 (p.Ala19Ser and p.His669Arg). Login to comment
132 The majority of X-ALD patients in our study group had non-recurrent (89%) mutations, except two patient (one of them Argentinean and the other of Italian origin) that had the same mutation p.His669Arg. Login to comment
150 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). Login to comment
155 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). Login to comment
157 On the other hand according to the literature when the change p.His669Arg is present, ALDP was not observed in western blot. Login to comment
158 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. Login to comment

PMID: 23768953 [PubMed] Petrillo S et al: "Glutathione imbalance in patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

74 Subject Age (years) Phenotype Mutation HAAM 4 CCALD c.1415_1416delAG (p.Q472RfsX83) AM 24 CCALD c.919C>T (p.Q307X) SM 16 CCALD c.1888G>A (p.E630K) ON 11 CCALD c.1628C>T (p.P543L) MG 62 AMN c.2006A>G (p.H669R) AG 33 AMN c.427C>T (p.P143S) BM 64 AMN c.1382delT (p.L461RfsX97) PF 54 AMN c.1252C>T (p.R418W) RN 61 AMN c.1415_1416delAG (p.Q472RfsX83) ME 20 AMN c.442_444 del 3(AAC)/ins6 (TGTTGA) (p.N148CfsX1) SF 40 AMN c.442_444 del 3(AAC)/ins6 (TGTTGA) (p.N148CfsX1) LM 54 AMN c.1540A>C (p.S514R) LF 43 AMN c.1415_1416delAG (p.Q472RfsX83) LM 40 AMN c.1415_1416delAG (p.Q472RfsX83) 2.5. 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
78 This missense allele involved the replacement of a histidine by an arginine at position 669 of ABCD1 (p.His669Arg).24 In addition, a single nucleotide polymorphism, c.1992-32c/t (refSNP: rs4898368), localized to intron 9 of the ABCD1 gene, was also observed among Taiwanese and Malaysian populations (Table 2). 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