ABCB6 p.Ser322Lys
| Predicted by SNAP2: | A: N (78%), C: N (82%), D: N (57%), E: N (57%), F: N (61%), G: N (87%), H: N (61%), I: N (66%), K: N (57%), L: N (66%), M: N (82%), N: N (82%), P: N (57%), Q: N (78%), R: N (53%), T: N (93%), V: N (66%), W: D (75%), Y: N (53%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: N, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: D, R: D, T: N, V: D, W: D, Y: D, |
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[hide] Genome-wide linkage, exome sequencing and function... PLoS One. 2014 Feb 3;9(2):e87250. doi: 10.1371/journal.pone.0087250. eCollection 2014. Liu H, Li Y, Hung KK, Wang N, Wang C, Chen X, Sheng D, Fu X, See K, Foo JN, Low H, Liany H, Irwan ID, Liu J, Yang B, Chen M, Yu Y, Yu G, Niu G, You J, Zhou Y, Ma S, Wang T, Yan X, Goh BK, Common JE, Lane BE, Sun Y, Zhou G, Lu X, Wang Z, Tian H, Cao Y, Chen S, Liu Q, Liu J, Zhang F
Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.
PLoS One. 2014 Feb 3;9(2):e87250. doi: 10.1371/journal.pone.0087250. eCollection 2014., [PMID:24498303]
Abstract [show]
BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.
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5 Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C.T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A.C; p.Ser322Lys) in one of the four families.
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ABCB6 p.Ser322Lys 24498303:5:223
status: NEW46 A new coding mutation in exon 4 (chr2:220081092, c.964A.C; p.Ser322Lys) was discovered in Family 2, which was heterozygous in all the seven affected individuals and absent in all the seven unaffected members (Figure 2A).
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ABCB6 p.Ser322Lys 24498303:46:61
status: NEW87 Sequence comparison of ABCB6 across different species showed that both the amino acids affected by DUH mutations (c.1358c.T;p.Ala453Val and c.964A.C; p.Ser322Lys) are highly conserved (Figure 2B), implying that these two residues are key to normal biological function of ABCB6.
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ABCB6 p.Ser322Lys 24498303:87:152
status: NEW100 A: Two mutations in ABCB6 and their sequencing traces, including c.1358C.T; p.Ala453Val in the Family 1 and c.964A.C; p.Ser322Lys in the Family 2; Arrows indicate the location of the two mutations.
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ABCB6 p.Ser322Lys 24498303:100:120
status: NEW[hide] Novel missense mutations of ABCB6 in two chinese f... J Dermatol Sci. 2014 Dec;76(3):255-8. doi: 10.1016/j.jdermsci.2014.08.015. Epub 2014 Sep 11. Lu C, Liu J, Liu F, Liu Y, Ma D, Zhang X
Novel missense mutations of ABCB6 in two chinese families with dyschromatosis universalis hereditaria.
J Dermatol Sci. 2014 Dec;76(3):255-8. doi: 10.1016/j.jdermsci.2014.08.015. Epub 2014 Sep 11., [PMID:25288164]
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51 frameshift mutations in ABCB6 have been reported to be responsible for DUH (p.S170G, p.S322K, p.L356P, p.A453V, p.Q555K, p.G579E and c.459delC) [6-8].
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ABCB6 p.Ser322Lys 25288164:51:87
status: NEW