ABCC6 p.Met848Val
| Predicted by SNAP2: | A: N (53%), C: D (71%), D: D (91%), E: D (85%), F: D (75%), G: D (85%), H: D (85%), I: D (71%), K: D (91%), L: D (71%), N: D (85%), P: D (91%), Q: D (80%), R: D (85%), S: D (66%), T: D (80%), V: N (72%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Spectrum of genetic variation at the ABCC6 locus i... J Dermatol Sci. 2009 Jun;54(3):198-204. Epub 2009 Mar 31. Ramsay M, Greenberg T, Lombard Z, Labrum R, Lubbe S, Aron S, Marais AS, Terry S, Bercovitch L, Viljoen D
Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals.
J Dermatol Sci. 2009 Jun;54(3):198-204. Epub 2009 Mar 31., [PMID:19339160]
Abstract [show]
BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder with ectopic mineralization in the skin, eyes and cardiovascular system. PXE is caused by mutations in ABCC6. OBJECTIVE: To examine 54 unrelated South African PXE patients for ABCC6 PXE causing mutations. METHODS: Patients were screened for mutations in ABCC6 using two strategies. The first involved a comprehensive screening of all the ABCC6 exons and flanking regions by dHPLC or sequencing whereas the second involved screening patients only for the common PXE mutations. The ABCC6 gene was screened in ten white and ten black healthy unrelated South Africans in order to examine the level of common non-PXE associated variation. RESULTS: The Afrikaner founder mutation, R1339C, was present in 0.41 of white ABCC6 PXE alleles, confirming the founder effect and its presence in both Afrikaans- (34/63 PXE alleles) and English-speakers (4/28). Eleven mutations were detected in the white patients (of European origin), including two nonsense mutations, 6 missense mutations, two frameshift mutations and a large deletion mutation. The five "Coloured" patients (of mixed Khoisan, Malay, European and African origin) included three compound heterozygotes with R1339C as one of the mutations. The three black patients (sub-Saharan African origin) were all apparent homozygotes for the R1314W mutation. Blacks showed a trend towards a higher degree of neurtral variation (18 variants) when compared to whites (12 variants). CONCLUSION: Delineation of the ABCC6 mutation profile in South African PXE patients will be used as a guide for molecular genetic testing in a clinical setting and for genetic counselling.
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No. Sentence Comment
133 With regard to neutral variation, all three PXE patients were homozygous for four neutral variants, indicating that they shared the same PXE haplotypes (N411N (c.1233 T>C - C allele); V415V (c.1245 G>C - C allele); G800G (c.2400 A>G - G allele); M848V (c.2542 A>G - G allele) and R1314W (T allele)).
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ABCC6 p.Met848Val 19339160:133:246
status: NEW149 998+13C>T - Intron - 1 - This study E 10 c.1233T>C N411N CL3 1 2 1 [32,35] rs9930886 E 10 c.1245G>A V415V CL4 - 2 - [32,35] rs9940825 E 10 c.1249G>A V417M CL4 5 - - This study IVS 10 c.1338+7C>G - Intron - 5 - [32] rs9940089 E 11 c.1344G>A L448L EL5 - 2 - This study IVS 11 c.1432-41A>C - Intron 3 1 2 [7,32] rs2239322 IVS 11 c.1432-45C>T - Intron - - 2 [11] No rs number IVS 11 c.1432-48G>A - Intron 7 - 8 dbSNP rs7193932 E 12 c.1494G>A K499K CL4 - - 1 This study IVS 12 c.1635+48C>T** - Intron 7 - - [32] ENSSNP11084760 E 14 c.1841T>C V614A CL5 15 2 3 [7,32,35] rs12931472 E 15 c.1890C>G T630T CL5 6 3 1 [32,35] rs8058696 E 16 c.1896C>A H632Q CL5 - 3 1 [31,32,36] rs8058694 E 17 c.2171G>A*** R724L NBF1 - 1 - [32] No rs number E 17 c.2175A>T V725V NBF1 - 2 - [32] No rs number E 17 c.2224A>G I742V NBF1 - 1 - [32] No rs number E 18 c.2400A>G G800G NBF1 1 2 - dbSNP rs7500834 E 19 c.2490C>T A830A CL6 3 - - [7,32] rs9924755 E 19 c.2542A>G M848V CL6 1 3 - dbSNP rs6416668 E 22 c.2835C>T P945P TS12 1 2 1 [32,37] rs2856585 E 22 c.2836C>A L946I TS12 1 - - This studya IVS 24 c.3507-16T>C - Intron 3 2 - [11,32] rs3213471 a L946I was previously identified as a pathogenic mutation by Morcher et al. [38], in this study bioinformatic analysis of the variant did not support a functional effect of the variant on the protein.
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ABCC6 p.Met848Val 19339160:149:940
status: NEW[hide] Acquired pseudoxanthoma elasticum presenting after... J Am Acad Dermatol. 2011 May;64(5):873-8. Epub 2011 Mar 12. Bercovitch L, Martin L, Chassaing N, Hefferon TW, Bessis D, Vanakker O, Terry SF
Acquired pseudoxanthoma elasticum presenting after liver transplantation.
J Am Acad Dermatol. 2011 May;64(5):873-8. Epub 2011 Mar 12., [PMID:21397982]
Abstract [show]
BACKGROUND: Pseudoxanthoma elasticum (PXE) is thought to be a metabolic disorder resulting from mutations in the gene encoding the cellular transporter, ABCC6, which is primarily expressed in liver and kidney. We encountered 3 patients who developed clinical and histopathological evidence of PXE after liver transplantation, suggesting that PXE could have been acquired from the transplanted organ. OBJECTIVE: We sought to delineate the clinical features and screen each patient and samples of donor liver for mutations in the ABCC6 gene. METHODS: Each patient underwent full clinical examination, skin biopsy, and ophthalmologic examination, and whole genome sequencing using standard techniques. Fixed samples of donor liver tissue were available for mutation analysis in two patients and of donor kidney tissue in one. RESULTS: All 3 patients had unequivocal clinical and histopathologic evidence of PXE. No patient (or family member available for screening) had evidence of mutations in ABCC6. Neither liver specimen nor the single available kidney specimen showed evidence of mutations in ABCC6. LIMITATIONS: Liver tissue was not available from one patient and DNA was of poor quality in another, resulting in limited screening. Genetic testing does not detect ABCC6 mutations in 10% of patients with confirmed PXE. CONCLUSION: Although we were unable to demonstrate ABCC6 mutations in limited screening of fixed donor livers, the absence of any PXE mutations in the affected patients, the timing of onset of PXE, and the known acquisition of other metabolic disorders and coagulopathies from donor livers suggest that PXE was likely acquired via liver transplantation.
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No. Sentence Comment
87 Analysis disclosed amino acid changing variants p.Ala158Val (c.437C[T) in exon 4, and HapMap polymorphism p.Met848Val (c.2542A[G) in exon 20. p.Ala158Val is a pseudogene variant that may have been detected as a result of nonspecific PCR product, whereas V848 is the vastly more common allele at this position.
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ABCC6 p.Met848Val 21397982:87:108
status: NEW