ABCD1 p.Ser514Arg
| Predicted by SNAP2: | A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, T: D, V: D, W: D, Y: D, |
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[hide] Identification of seven novel mutations in ABCD1 b... Hum Mutat. 2005 Feb;25(2):222. Montagna G, Di Biase A, Cappa M, Melone MA, Piantadosi C, Colabianchi D, Patrono C, Attori L, Cannelli N, Cotrufo R, Salvati S, Santorelli FM
Identification of seven novel mutations in ABCD1 by a DHPLC-based assay in Italian patients with X-linked adrenoleukodystrophy.
Hum Mutat. 2005 Feb;25(2):222., [PMID:15643618]
Abstract [show]
We report the molecular findings in 14 patients (12 families) with X-linked adrenoleukodystrophy (X-ALD, MIM# 300100), a well-defined peroxisomal disorder attributed to mutations in the ABCD1 gene on chromosome Xq28. With the aims of determining the spectrum of mutations and developing an efficient molecular genetic test for analysis of at-risk women whose carrier status is unknown, and to offer molecular confirmation of their status to obligate heterozygotes, regardless of their clinical status, we carried out molecular screening by setting up a denaturing high-performance liquid chromatography (DHPLC)-based protocol. We identified eleven hemizygous base changes in ABCD1, including seven new mutations (c.145underscore;146ins4, c.264C>G, c.919C>T, c.994C>T, c.1027G>A, c.1508T>C, and c.1540A>C, resulting in the p.Pro193fs, p.Cys88Trp, p.Gln307X, p.Gln332X, p.Gly343Ser, p.Leu503Pro, and p.Ser514Arg changes, respectively). Adding new variants to the repertoire of ABCD1 mutations in X-ALD, our data provide an efficient, cost-effective, and reliable DHPLC detection protocol for mutation screening of X-ALD families.
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4 We identified eleven hemizygous base changes in ABCD1, including seven new mutations (c.145_146ins4, c.264C>G, c.919C>T, c.994C>T, c.1027G>A, c.1508T>C, and c.1540A>C, resulting in the p.Pro193fs, p.Cys88Trp, p.Gln307X, p.Gln332X, p.Gly343Ser, p.Leu503Pro, and p.Ser514Arg changes, respectively).
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ABCD1 p.Ser514Arg 15643618:4:263
status: NEW95 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.
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ABCD1 p.Ser514Arg 15643618:95:391
status: NEW101 However, the p.Ser514Arg mutation was found in two families who denied formal consanguinity.
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ABCD1 p.Ser514Arg 15643618:101:15
status: NEW[hide] Glutathione imbalance in patients with X-linked ad... Mol Genet Metab. 2013 Aug;109(4):366-70. doi: 10.1016/j.ymgme.2013.05.009. Epub 2013 May 22. Petrillo S, Piemonte F, Pastore A, Tozzi G, Aiello C, Pujol A, Cappa M, Bertini E
Glutathione imbalance in patients with X-linked adrenoleukodystrophy.
Mol Genet Metab. 2013 Aug;109(4):366-70. doi: 10.1016/j.ymgme.2013.05.009. Epub 2013 May 22., [PMID:23768953]
Abstract [show]
BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition. METHODS: Lymphocytes, plasma and erythrocytes were obtained from the whole blood of 14 subjects with X-ALD and in 30 healthy subjects. Total, reduced and protein-bound glutathione levels were measured in lymphocytes by HPLC analysis. Erythrocyte free glutathione and antioxidant enzyme activities, plasma thiols and carbonyl content were determined by spectrophotometric assays. RESULTS: A significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms. A decline of free glutathione was particularly significant in erythrocytes. The increased oxidative stress in X-ALD was additionally confirmed by the decrease of plasma thiols and the high level of carbonyls. CONCLUSION: Our results strongly support a role for oxidative stress in the pathophysiology of X-ALD and strengthen the importance of the balance among glutathione forms as a hallmark and a potential biomarker of the disease.
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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.
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ABCD1 p.Ser514Arg 23768953:74:487
status: NEW