ABCD1 p.Gly343Val
| Predicted by SNAP2: | A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: 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%), S: 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, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Molecular diagnosis of X-linked adrenoleukodystrop... Clin Chim Acta. 2011 May 12;412(11-12):970-4. Epub 2011 Feb 12. Lan F, Wang Z, Xie H, Huang L, Ke L, Yang B, Zhu Z
Molecular diagnosis of X-linked adrenoleukodystrophy: experience from a clinical genetic laboratory in mainland China with report of 13 novel mutations.
Clin Chim Acta. 2011 May 12;412(11-12):970-4. Epub 2011 Feb 12., [PMID:21300044]
Abstract [show]
BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by progressive demyelination of the nervous system, adrenocortical insufficiency and increase of very long chain fatty acids (VLCFAs) in the plasma and tissues. METHODS: A total of 131 individuals from 30 Chinese pedigrees were involved in this study, including 42 symptomatic patients, 44 female carriers, and 15 high-risk fetuses from 13 families. The mutation was first pinpointed through long distance RT-PCR-based RNA approach and confirmed through peripheral blood DNA approach. RESULTS: A total of 28 mutations were identified, of which 19 were missense, 3 nonsense and 6 frame-shift mutations. Thirteen mutations were novel, i.e. p.R280L, p.P580L, p.G343V, p.S108X, p.R259W, p.P534R, p.fs A246, p.L576P, p.K602X, p.A314P, p.N148D, p.H283R, and p.fs R89. Two mutations occurred de novo, for they were not found in somatic cells of their parents. Three females from the same family developed AMN-like symptoms and they were heterozygous for the p.H283R mutation. Four asymptomatic boys were diagnosed as X-ALD patients and prenatal molecular diagnosis were provided for 13 X-ALD-stricken families. CONCLUSIONS: Our work extended the spectrum of mutations in X-ALD and benefited genetic counseling through reliable identification of heterozygous females and asymptomatic males.
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No. Sentence Comment
4 Thirteen mutations were novel, i.e. p.R280L, p.P580L, p.G343V, p.S108X, p.R259W, p.P534R, p.fs A246, p.L576P, p.K602X, p.A314P, p.N148D, p.H283R, and p.fs R89.
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ABCD1 p.Gly343Val 21300044:4:56
status: NEW53 Thirteen mutations were novel, i.e. p.R280L, p.P580L, p.G343V, p.S108X, p.R259W, p.fs A246, p.L576P, p.P534R, p.K602X, p.A314P, p.N148D, p.H283R, and p.fs R89, 9 of which were missense mutations.
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ABCD1 p.Gly343Val 21300044:53:56
status: NEW99 Pedigree Number of patient Number of carriere Phenotype of patient Base change Amino acid change Position of mutation Feature of mutation Prenatal diagnosis 1 1 2 AdolCALD 1225GNT R280L Exon 1 Missense 2 1 1 CCALD 1909CNT P508L Exon 6 Missense 3 4 3 CCALD 1987CNG P534R Exon 6 Missense Y 4 1 1 CCALD 1182GNA G266R Exon 1 Missense 5 1a +1b 1 CCALD 2235CNG R617G Exon 8 Missense Y 6 1+1a +1c 1 CCALD 1414GNT G343V Exon 2 Missense 7 1 1 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift 8 1+1b 1 CCALD 2235CNT R617C Exon 8 Missense Yh 9 1 1 CCALD 2065CNT P560L Exon 7 Y 10 1+1a 2+1b CCALD [709 NA; 1161CNT] [S108X; R259W] Exon 1 Nonsense; Missense Y 11 1 1 CCALD 1126ins GCCATCG fs I246 Exon 1 Frameshift 12 1 1 CCALD 2113TNC L576P Exon 7 Missense 13 1a +2c 3 CCALD 807GNA A141T Exon 1 Missense 14 1 1 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift Y 15 1 1+1b CCALD 915CNA Q177X Exon 1 Nonsense Yh 16 1+1a 1 CCALD 1588GNA R401Q Exon 3 Missense 17 1 1 CCALD 1212 ANG K276E Exon 1 Missense Y 18 1 1 CCALD 907 ANG Y174C Exon 1 Missense 19 1 2 CCALD 2190 ANT K602X Exon 8 Nonsense 20 1 1 CCALD 1326GNC A314P Exon 2 Missense 21 1 1 CCALD 828 ANG N148D Exon 1 Missense Y 22 1 1 CCALD 1588GNA R401Q Exon 3 Missense Y 23 1 0f CCALD 2278GNA C631Y Exon 9 Missense 24 1a 1 CCALD 1008insG fs S207 Exon 1 Frameshift Y 25 1 0f CCALD 1920GNA G512S Exon 6 Missense 26 1+1c 3 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift Y 27 1+1b 1 CCALD [1035ANG; 1853GNA] [K217E; V489V] Exon 1 Missense; same sense Y 28 1+3d 4 AMNg 1234ANG H283R Exon 1 Missense 29 1+2a 3 CCALD 1233CNG H283D Exon 1 Missense 30 2 3 AMN; CCALD 656_57 delGA fs R89 Exon 1 Frameshift a patient or proband died at the time of referral; b fetus by prenatal diagnosis; c presymptomatic at the time of referral; d female heterozygote patient; e determined by molecular ananlysis or deduced by the fact that the carrier was the daughter of an X-ALD, or the mother of at least one X-ALD patients; f de novo mutation; g including three heterozygote female patients; h twice for two pregnancies.
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ABCD1 p.Gly343Val 21300044:99:406
status: NEW[hide] Pre-symptomatic molecular diagnosis of X-linked ad... Neurol Res. 2010 Sep;32(7):695-9. Epub 2009 Aug 5. Wang Z, Ke L, Xie H, Yan A, Huang L, Lan F
Pre-symptomatic molecular diagnosis of X-linked adrenoleukodystrophy in Chinese families.
Neurol Res. 2010 Sep;32(7):695-9. Epub 2009 Aug 5., [PMID:19660195]
Abstract [show]
OBJECTIVE: To identify asymptomatic males with X-linked adrenoleukodystrophy (X-ALD) from Chinese pedigrees by molecular genetic testing. METHODS: Genomic DNA was extracted from peripheral blood of the asymptomatic individuals from X-ALD families, and fragments spanning the proband's mutation were amplified. PCR-RFLP, direct sequencing and denaturing high performance liquid chromatography (DHPLC) were used to detect the PCR products. RESULTS: Four asymptomatic male subjects from three Chinese X-ALD pedigrees were found to carry the same mutation with the probands. In Pedigree 1, by restriction analysis with endonuclease Eco47 I, the digestion pattern of the proband's elder brother (Subject 1) was same with the proband, which indicated that both carried the same mutation. In Pedigree 2 and Pedigree 3, the PCR products were analysed by DHPLC, and the patterns of elution peaks of the Subjects 2-4 and the heterozygous mothers were similar, which indicated the presence of sequence alterations in the ABCD1 gene. DNA sequencing of the corresponding PCR products confirmed the mutations. CONCLUSIONS: Molecular testing was an effective way to determine the genotype of family members of X-ALD before they develop any symptoms. Early and preferable pre-symptomatic identification of hemizygotes is of great benefit to affected individuals and their families.
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No. Sentence Comment
29 Proband 1 was diagnosed with cerebral X-ALD at the age of 11 years, and G343V mutation was identified in the ABCD1 gene of him and his mother in our laboratory.
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ABCD1 p.Gly343Val 19660195:29:72
status: NEW39 Fragments that covered the G343V mutation (Pedigree 1), A141T mutation (Pedigree 2) or fsGlu471 mutation (Pedigree 3) of the ABCD1 gene were amplified with the primers listed in Table 1.
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ABCD1 p.Gly343Val 19660195:39:27
status: NEW43 Restrictive digestion Mutation G343V gives rise to an additional Eco47 I restriction site within the corresponding segment amplified, which allows for the application of restriction fragment length polymorphism (RFLP) analysis to reveal the mutation.
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ABCD1 p.Gly343Val 19660195:43:31
status: NEW51 Results Restrictive analysis and DNA sequencing in Pedigree 1 In restriction analysis with endonuclease Eco47 I digestion, the digestion pattern of Subject 1 was found to be identical to that of Proband 1 (Figure 1A), which indicated that both carried the same mutation G343V (GGCRGTC).
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ABCD1 p.Gly343Val 19660195:51:270
status: NEW63 In Pedigree 1, the mutation found in Subject 1 (G343V) was a novel mutation identified in our laboratory16 , while the mutation found in Subjects 2 and 3 (A141T) of Pedigree 2 and the mutation found in Subject 4 (fsGlu471) of Pedigree 3 have been identified by other authors as pathogenic mutations.
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ABCD1 p.Gly343Val 19660195:63:48
status: NEW72 (B) DNA sequencing confirmed the G343V mutation (GGCRGTC) in Subject 1.
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ABCD1 p.Gly343Val 19660195:72:33
status: NEW[hide] ABCD1 gene mutations in Chinese patients with X-li... Pediatr Neurol. 2005 Aug;33(2):114-20. Pan H, Xiong H, Wu Y, Zhang YH, Bao XH, Jiang YW, Wu XR
ABCD1 gene mutations in Chinese patients with X-linked adrenoleukodystrophy.
Pediatr Neurol. 2005 Aug;33(2):114-20., [PMID:16087056]
Abstract [show]
X-linked adrenoleukodystrophy is a neurodegenerative disorder caused by mutations in the adrenoleukodystrophy (ALD) protein gene ABCD1. This study used direct sequencing of genomic polymerase chain reaction products to perform mutational analysis of ABCD1 in 34 unrelated Chinese X-linked adrenoleukodystrophy patients and 27 of their maternal relatives. Thirty-two different mutations were identified in 34 patients. Most of the mutations (62.5%, 20/32) were missense mutations, six of which are novel. One novel single nucleotide polymorphism, c.1047 C>A, was also found in three patients and their mothers, which can also be observed in 1 of 120 normal control alleles. Two synonymous mutations (p.L516L and p.V349V) appeared in two unrelated patients, and no other mutations were evident after screening the gene's 10 exons. Seventeen of the probands' mothers were found to be heterozygous for the same mutations present in their sons' ABCD1 gene. Eight of the 10 screened sisters and cousins were identified as carriers. There were no hot spot mutations in the ABCD1 gene of Chinese patients with X-linked adrenoleukodystrophy. However, over half of the mutations (19/34) were located in exon 1 and exon 6, suggesting possible hot exons. No obvious relationship between genotype and phenotype was observed.
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62 The GϾA substitution at codon 510 (p.G510D), and the GϾT substitution at codon 343 (p.G343V), eliminated Bgl I and Ava I sites, respectively.
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ABCD1 p.Gly343Val 16087056:62:98
status: NEW63 However, the TϾA substitution at codon 605 (p. L605Q) generated a new BstX I restriction site.
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ABCD1 p.Gly343Val 16087056:63:98
status: NEW130 (a) c.1028 GϾT (p.G343V); (b) c.1529 CϾT (p.G510D, antisense strand); (c) c.1814 TϾA (p.L605Q); (d) c.385 insC (p.fs R128, antisense strand); (e) c.1603 delCC (p.fs P534); (f) c.240-241 ins9tcc, tgc,ggc (p.R80-L81insPAA).
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ABCD1 p.Gly343Val 16087056:130:24
status: NEW131 (a) c.1028 Gb0e;T (p.G343V); (b) c.1529 Cb0e;T (p.G510D, antisense strand); (c) c.1814 Tb0e;A (p.L605Q); (d) c.385 insC (p.fs R128, antisense strand); (e) c.1603 delCC (p.fs P534); (f) c.240-241 ins9tcc, tgc,ggc (p.R80-L81insPAA).
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ABCD1 p.Gly343Val 16087056:131:24
status: NEW[hide] ABCD1 mutations and phenotype distribution in Chin... Gene. 2013 Jun 10;522(1):117-20. doi: 10.1016/j.gene.2013.03.067. Epub 2013 Apr 5. Niu YF, Ni W, Wu ZY
ABCD1 mutations and phenotype distribution in Chinese patients with X-linked adrenoleukodystrophy.
Gene. 2013 Jun 10;522(1):117-20. doi: 10.1016/j.gene.2013.03.067. Epub 2013 Apr 5., [PMID:23566833]
Abstract [show]
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder resulting from mutations within the ABCD1 gene. Adrenomyeloneuropathy (AMN) and childhood cerebral ALD (CCALD) are most common phenotypes in the Western ALD patients. Here we performed mutation analysis of ABCD1 in 10 Chinese ALD families and identified 8 mutations, including one novel deletion (c.1477_1488+11del23) and 7 known mutations. Mutations c.1772G>A and c.1816T>C were first reported in the Chinese patients. Mutations c.1661G>A and c.1679C>T were demonstrated to be de novo mutations. The dinucleotide deletion 1415_16delAG, described as a mutational hotspot in different ethnic groups, was identified in two families. In addition, we performed a retrospective nation-wide mutation study of X-linked ALD in China based on a literature review. The retrospective study further confirmed the hypothesis that exon 6 is a potential mutation cluster region in the Asian populations. Furthermore, it suggested that CCALD is the most common phenotype in China.
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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.
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ABCD1 p.Gly343Val 23566833:74:187
status: NEW