ABCD1 p.Leu322Pro
| Predicted by SNAP2: | A: N (66%), C: N (72%), D: D (66%), E: N (57%), F: N (66%), G: D (59%), H: D (53%), I: N (61%), K: D (59%), M: N (66%), N: D (59%), P: D (75%), Q: N (57%), R: D (63%), S: N (66%), T: N (61%), V: N (72%), W: D (66%), Y: N (66%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] A novel mutation found in an adrenoleukodystrophy ... J Inherit Metab Dis. 1998 Apr;21(2):162-6. Osaka H, Sekiguchi H, Inoue K, Ikuta K, Sakakihara Y, Oka A, Onishi H, Miyakawa T, Suzuki K, Kimura S, Kosaka K, Matsuyama S
A novel mutation found in an adrenoleukodystrophy patient who underwent bone marrow transplantation.
J Inherit Metab Dis. 1998 Apr;21(2):162-6., [PMID:9584268]
Abstract [show]
We identified a novel mutation, L322P, in a patient with X-linked adrenoleukodystrophy (ALD) who underwent bone marrow transplantation (BMT). An identification of the ALD gene mutation enabled us to employ an approach not dependent on the use of radioisotopes for detecting mixed chimerism. This assay could show more than 99.0% of the patient's peripheral white blood cells were replaced by the donor's cells.
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No. Sentence Comment
33 We conÐrmed the absence of this L322P mutation in 75 unrelated Japanese individuals by restriction analysis.
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ABCD1 p.Leu322Pro 9584268:33:37
status: NEW57 The L322P mutation, residing in a hydrophobic region, also a†ects the amino acid common to ALD protein and 70K PMP.
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ABCD1 p.Leu322Pro 9584268:57:4
status: NEW58 We could not Ðnd this L322P mutation in Japanese normal controls; it is likely to be a mutation that causes ALD.
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ABCD1 p.Leu322Pro 9584268:58:27
status: NEW[hide] Decreased expression of ABCD4 and BG1 genes early ... Hum Mol Genet. 2005 May 15;14(10):1293-303. Epub 2005 Mar 30. Asheuer M, Bieche I, Laurendeau I, Moser A, Hainque B, Vidaud M, Aubourg P
Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy.
Hum Mol Genet. 2005 May 15;14(10):1293-303. Epub 2005 Mar 30., [PMID:15800013]
Abstract [show]
Childhood cerebral adrenoleukodystrophy (CCER), adrenomyeloneuropathy (AMN) and AMN with cerebral demyelination (AMN-C) are the main phenotypic variants of X-linked adrenoleukodystrophy (ALD). It is caused by mutations in the ABCD1 gene encoding a half-size peroxisomal transporter that has to dimerize to become functional. The biochemical hallmark of ALD is the accumulation of very-long-chain fatty acids (VLCFA) in plasma and tissues. However, there is no correlation between the ALD phenotype and the ABCD1 gene mutations or the accumulation of VLCFA in plasma and fibroblast from ALD patients. The absence of genotype-phenotype correlation suggests the existence of modifier genes. To elucidate the mechanisms underlying the phenotypic variability of ALD, we studied the expression of ABCD1, three other peroxisomal transporter genes of the same family (ABCD2, ABCD3 and ABCD4) and two VLCFA synthetase genes (VLCS and BG1) involved in VLCFA metabolism, as well as the VLCFA concentrations in the normal white matter (WM) from ALD patients with CCER, AMN-C and AMN phenotypes. This study shows that: (1) ABCD1 gene mutations leading to truncated ALD protein are unlikely to cause variation in the ALD phenotype; (2) accumulation of saturated VLCFA in normal-appearing WM correlates with ALD phenotype and (3) expression of the ABCD4 and BG1, but not of the ABCD2, ABCD3 and VLCS genes, tends to be correlated with the severity of the disease, acting early in the pathogenesis of ALD.
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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).
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ABCD1 p.Leu322Pro 15800013:76:753
status: NEW[hide] Mutational analyses on X-linked adrenoleukodystrop... Pediatr Neurol. 2013 Sep;49(3):185-90. doi: 10.1016/j.pediatrneurol.2013.04.021. Epub 2013 Jul 5. Hung KL, Wang JS, Keng WT, Chen HJ, Liang JS, Ngu LH, Lu JF
Mutational analyses on X-linked adrenoleukodystrophy reveal a novel cryptic splicing and three missense mutations in the ABCD1 gene.
Pediatr Neurol. 2013 Sep;49(3):185-90. doi: 10.1016/j.pediatrneurol.2013.04.021. Epub 2013 Jul 5., [PMID:23835273]
Abstract [show]
BACKGROUND: X-linked adrenoleukodystrophy is caused by a defective peroxisomal membrane transporter, ABCD1, responsible for transporting very-long-chain fatty acid substrate into peroxisomes for degradation. The main biochemical defect, which is also one of the major diagnostic hallmarks, of X-linked adrenoleukodystrophy is the accumulation of saturated very-long-chain fatty acids in all tissues and body fluids. METHODS: Direct and reverse-transcribed polymerase chain reactions followed by DNA sequencing-based mutational analyses were performed on one Taiwanese and three Malaysian X-linked adrenoleukodystrophy families. RESULTS: A novel splicing donor site mutation (c.1272+1g>a) was identified in a Taiwanese X-linked adrenoleukodystrophy patient, resulting in a deletion of 121 bp and a premature stop codon (p.Val425fs*92) in messenger-RNA transcript. This deletion is caused by the activation of a cryptic splicing donor site in exon 4 of the ABCD1 gene, which is consistent with the prediction by several online algorithms. 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. CONCLUSIONS: This is the first report to unveil unequivocally that cryptic splicing-induced aberrant messenger-RNA carrying an internal frameshift deletion results from an intronic mutation in the ABCD1 gene. Furthermore, a polymorphism in intron 9 (c.1992-32c/t; refSNP: rs4898368) of the ABCD1 gene was commonly observed in both Taiwanese and Malaysian populations.
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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.
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ABCD1 p.Leu322Pro 23835273:5:128
status: NEW56 Mutational analysis on genomic DNA revealed a T-to-C transition mutation (c.965T>C) at exon 2 of the ABCD1 gene, leading to the substitution of a leucine at position 322 to a proline (p.Leu322Pro) in ABCD1 (Fig 2).19,20 This transition mutation created a BspEI restriction site (50-T/CCGGA-30) from the original 50-TCTGGA-30 sequence, which can be useful for rapid screening of the mutant allele.
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ABCD1 p.Leu322Pro 23835273:56:146
status: NEWX
ABCD1 p.Leu322Pro 23835273:56:186
status: NEW98 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.
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ABCD1 p.Leu322Pro 23835273:98:94
status: NEW113 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.
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ABCD1 p.Leu322Pro 23835273:113:107
status: NEW