ABCMdb

PMID: 24498303

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., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCB6 p.Ala453Val 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. Login to comment 5 ABCB6 p.Ala453Val ABCB6 p.Ser322Lys 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. Login to comment 40 ABCB6 p.Ala453Val This coding mutation (c.1358C.T; p.Ala453Val) is in the exon 7 of ABCB6, and was predicted to be damaging by SIFT and probably damaging by PolyphenII. Login to comment 42 ABCB6 p.Ala453Val Sanger Sequencing to Verify the Candidate Gene ABCB6 To verify the mutation (c.1358C.T; p.Ala453Val), 13 individuals of the Family 1 (Figure 1A) were Sanger sequenced for all the exons of ABCB6. Login to comment 46 ABCB6 p.Ser322Lys 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). Login to comment 66 ABCB6 p.Leu811Val ABCB6 p.Ala57Thr Discussion A recent publication showed that two missense mutations of ABCB6 (c.2431C.G; p.Leu811Val and c.169G.A; p.Ala57Thr) caused ocular coloboma [10]. Login to comment 82 ABCB6 p.Leu811Val ABCB6 p.Ala57Thr The two DUH mutations lie in the ABC transmembrane domain, whereas one coloboma mutation (c.2431C.G; p.Leu811Val) located in the transporter-like domain, and the other one (c.169G.A; p.Ala57Thr) did not lie in any established domain (Figure 2 C). Login to comment 87 ABCB6 p.Ser322Lys 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. Login to comment 100 ABCB6 p.Ala453Val ABCB6 p.Ser322Lys 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. Login to comment 103 ABCB6 p.Leu811Val ABCB6 p.Ala57Thr ABCB6 p.Ala453Val ABCB6 p.Ser322Leu C: ABCB6 exon structure, where c.964A.C; p.S322L and c.1358C.T; p.A453V are DUH mutations identified in this paper, c.169G.A; p.A57T and c.2431C.G; p.L811V are coloboma mutations7 . Login to comment