ABCC6 p.Gly1481Ser
| LOVD-ABCC6: |
p.Gly1481Ser
D
|
| Predicted by SNAP2: | A: N (61%), C: D (71%), D: N (82%), E: D (53%), F: D (85%), H: D (85%), I: D (85%), K: D (91%), L: D (85%), M: D (85%), N: D (80%), P: D (91%), Q: N (53%), R: D (91%), S: D (71%), T: D (80%), V: D (80%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, E: N, F: D, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: N, R: D, S: N, T: D, V: D, W: D, Y: D, |
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[hide] Mutation detection in the ABCC6 gene and genotype-... J Med Genet. 2007 Oct;44(10):621-8. Epub 2007 Jul 6. Pfendner EG, Vanakker OM, Terry SF, Vourthis S, McAndrew PE, McClain MR, Fratta S, Marais AS, Hariri S, Coucke PJ, Ramsay M, Viljoen D, Terry PF, De Paepe A, Uitto J, Bercovitch LG
Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum.
J Med Genet. 2007 Oct;44(10):621-8. Epub 2007 Jul 6., [PMID:17617515]
Abstract [show]
BACKGROUND: Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder with considerable phenotypic variability, mainly affects the eyes, skin and cardiovascular system, characterised by dystrophic mineralization of connective tissues. It is caused by mutations in the ABCC6 (ATP binding cassette family C member 6) gene, which encodes MRP6 (multidrug resistance-associated protein 6). OBJECTIVE: To investigate the mutation spectrum of ABCC6 and possible genotype-phenotype correlations. METHODS: Mutation data were collected on an international case series of 270 patients with PXE (239 probands, 31 affected family members). A denaturing high-performance liquid chromatography-based assay was developed to screen for mutations in all 31 exons, eliminating pseudogene coamplification. In 134 patients with a known phenotype and both mutations identified, genotype-phenotype correlations were assessed. RESULTS: In total, 316 mutant alleles in ABCC6, including 39 novel mutations, were identified in 239 probands. Mutations were found to cluster in exons 24 and 28, corresponding to the second nucleotide-binding fold and the last intracellular domain of the protein. Together with the recurrent R1141X and del23-29 mutations, these mutations accounted for 71.5% of the total individual mutations identified. Genotype-phenotype analysis failed to reveal a significant correlation between the types of mutations identified or their predicted effect on the expression of the protein and the age of onset and severity of the disease. CONCLUSIONS: This study emphasises the principal role of ABCC6 mutations in the pathogenesis of PXE, but the reasons for phenotypic variability remain to be explored.
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No. Sentence Comment
277 Finally, there is the possibility that mutations in genes other than ABCC6 can Nucleotide change*À Predicted consequenceÀ Frequency (alleles) Exon-intron location Domain affected` Mutant alleles (%) References1 c.4041gRc p.Q1347H 1 28 NBF2 0.3 25 c.4104delC FS 1 29 0.3 25 c.4192cRt p.R1398X 2 29 0.6 25 c.4335delG FS 1 30 0.3 c.4441gRa p.G1481S 1 31 NBF2 0.3 c.4501gRa p.G1501S 1 31 NBF2 0.3 Ex23_29del p.A999_S1403del 57 23-29 18.0 15, 18, 21, 25, 27, 28, 31, 32, 37, 44, 45 FS, frameshift; IC, intracellular domain; IVS, intron; NBF, nucleotide binding fold; SJ, splice junction; TM, transmembrane domain.
X
ABCC6 p.Gly1481Ser 17617515:277:349
status: NEW