ABCMdb

PMID: 19284998

Sato N, Nakayama T, Mizutani Y, Yuzawa M
Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks.
Biochem Biophys Res Commun. 2009 Mar 13;380(3):548-53. Epub 2009 Jan 25., 2009-03-13 [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC6 p.Arg419Gln ABCC6 p.Glu422Lys ABCC6 p.Glu1427Lys Six variants were successfully identified as causal mutations for AS (p.R419Q, p.E422K, c.2542delG, Del_Exon23, c.3774-3775insC and p.E1427K), and 4 of these were novel. Login to comment 84 ABCC6 p.Arg1268Gln ABCC6 p.Val614Ala ABCC6 p.His632Gln ABCC6 p.Arg419Gln ABCC6 p.Glu1427Lys ABCC6 p.Ser587Cys ABCC6 p.Ala950Val We identified 8 nonsynonymous variants and a deletion variant in the exon regions; p.R419Q (Exon10), p.S587C (exon13), p.V614A (Exon14), p.H632Q (Exon15), c.2542delG (Exon19), p.A950V (Exon22), p.R1268Q (Exon27) and p.E1427K (Exon30). Login to comment 104 ABCC6 p.Arg1268Gln ABCC6 p.Val614Ala ABCC6 p.His632Gln ABCC6 p.Arg419Gln Disease-causing mutations The homozygous p.R419Q and the homozygous p.R1268Q were found in 2 subjects with the homozygous GTGG/GTGG diplotype. The homozygous c.2542delG and the homozygous p.H632Q or homozygous p.V614A were found in each subject with the homozygous ATGA/ATGA diplotype. The homozygous Del_Exon23 was found in 2 subjects with the homozygous GTGA/GTGA diplotype. Login to comment 106 ABCC6 p.Arg1268Gln ABCC6 p.Val614Ala ABCC6 p.Val614Ala ABCC6 p.His632Gln ABCC6 p.His632Gln ABCC6 p.Glu1427Lys ABCC6 p.Ser587Cys ABCC6 p.Ala950Val The heterozygous p.E1427K and p.V614A or p.H632Q or p.R1268Q were found in a subject with the heterozygous GTAA/ATGG diplotype. The heterozygous c.2542delG and p.V614A or p.H632Q were found in a subject with the heterozygous GTAA/ACAA diplotype. The heterozygous p.S587C was found in a subject with the heterozygous GTGA/GCGA diplotype, and the heterozygous p.A950V was found in a subject with the heterozygous GTAA/GCAA diplotype. Login to comment 109 ABCC6 p.Arg1268Gln ABCC6 p.Val614Ala ABCC6 p.His632Gln ABCC6 p.Ser587Cys ABCC6 p.Ala950Val Consequently, p.S587C (exon13), p.V614A (Exon14), p.H632Q (Exon15), p.A950V (Exon22) and p.R1268Q (Exon27) were excluded from among the disease-causing mutations because they were seen in the control group. Login to comment 110 ABCC6 p.Arg1268Gln ABCC6 p.Val614Ala ABCC6 p.His632Gln Of the 9 variants, p.V614A, p.H632Q and p.R1268Q were previously reported as non-causal variants for PXE. Although c.2542delG (Exon19) was seen in the control group, this is defined as the disease-causing mutation because it yields a premature stop codon. Login to comment 114 ABCC6 p.Arg419Gln ABCC6 p.Arg419Gln ABCC6 p.Arg419Gln ABCC6 p.Arg419Gln ABCC6 p.Arg419Gln ABCC6 p.Arg419Gln ABCC6 p.Glu422Lys ABCC6 p.Glu1427Lys ABCC6 p.Ser587Cys ABCC6 p.Ala950Val of patients PXE Non-PXE Unknown GTGG/GTGG 8 p.R419Q/p.R419Q 5 3 1 1 p.R419Q/À 1 0 0 1 À/À 2 0 0 2 GTGG/GTGA 8 p.R419Q/À 2 2 0 0 À/À 6 4 0 2 ATGA/ATGA 8 c.2542delG/c.2542delG 7 4 2 1 c.2542delG/À 1 1 0 0 GTGG/ATGA 5 c.2542delG/À 4 3 0 1 À/À 1 1 0 0 GTGA/GTGA 4 Del_Exon23/Del_Exon23 2 1 0 1 À/À 2 2 0 0 GTAA/GTAA 3 À/À 3 3 0 0 ATGA/GTGA 3 c.2542delG/À 2 2 0 0 À/À 1 0 0 1 ATGA/GTAA 3 p.E422K/c.2542delG 1 1 0 0 c.2542delG/À 1 1 0 0 À/À 1 0 0 1 GTGA/GTAA 2 À/À 2 1 1 0 GTAA/ACAA 2 c.2542delG/À 2 2 0 0 GTGG/GCGA 1 À/À 1 1 0 0 GTGG/ATGG 1 p.R419Q/p.R419Q 1 0 0 1 GTGA/GCGA 1 p.S587C/À 1 0 1 0 GTGA/GCAA 1 À/À 1 1 0 0 GTGA/ACAA 1 c.2542delG/c.3774-3775insC 1 0 1 0 GTAA/GCAA 1 p.A950V/À 1 0 1 0 GTAA/ATGG 1 p.E1427K/À 1 0 0 1 ATGA/ATGG 1 c.2542delG/À 1 1 0 0 For ABCC6 proteins, the designations for the mutations refer to the position of the amino acid substitution, where amino acid terminus. Nonsynonymous variants were shown by the amino acid numbers started by the strat codon methionine. The cDNA base numbers refer to the nucleotide in the cDNA, where nucleotide 1 is the A of the first ATG. Exon22 Exon23 Exon24 Wile Type 32nortnI22nortnI Exon22 Exon24 Mutation Type Intron23Intron22 Breakpoint (3901bp Deletion) Fig. 3. Login to comment 119 ABCC6 p.Arg419Gln ABCC6 p.Glu422Lys ABCC6 p.Glu1427Lys ABCC6 p.Ser587Cys ABCC6 p.Ala950Val The most common alleles were c.2542delG (25.0%), p.R419Q (13.9%), Del_Exon23 (3.7%), followed by c.3774-3775insC, p.E422K, p.S587C, p.A950V and p.E1427K (all 0.93%). Login to comment 120 ABCC6 p.Arg419Gln ABCC6 p.Arg419Gln ABCC6 p.Glu422Lys With regard to genotyping for each subject, 7 patients had c.2542delG/c.2542delG, 6 had p.R419Q/p.R419Q, 2 had Del_Exon23/Del_Exon23, 1 had c.2542delG/c.3774-3775insC and 1 had p.E422K/c.2542delG. Login to comment 121 ABCC6 p.Arg419Gln ABCC6 p.Glu1427Lys ABCC6 p.Ser587Cys ABCC6 p.Ala950Val There were 17 patients with only 1 allele, 11 patients with c.2542delG/À, 3 with p.R419Q/À, 1 with p.S587C/À, 1 with p.A950V/À and 1 with p.E1427K/À. Login to comment 123 ABCC6 p.Ser587Cys ABCC6 p.Ala950Val ABCC6 p.Asn428Ser ABCC6 p.Asn428Ser ABCC6 p.Val438Met The p.N428S/À, p.A950V/À, p.V438M/À, c.2542delG/À, p.S587C/À and p.N428S/À mutations were also seen in the control group. Login to comment 135 ABCC6 p.Arg419Gln The 3 most frequent alleles, c.2542delG (27 alleles), p.R419Q (15 alleles) and Del_Exon23 (4 alleles), accounted for more than 90%. Login to comment 137 ABCC6 p.Arg419Gln Of 15 p.R419Q alleles, 14 alleles were linked to the GTGG haplotype (14/15 = 93.3%), of 27 c.2542delG alleles, 24 alleles were linked to the ATGA haplotype (24/27 = 88.9%) and of 4 Del_Exon23 alleles, 4 alleles were linked to the GTGA haplotype (4/4 = 100%). Login to comment 157 ABCC6 p.Arg1268Gln ABCC6 p.Val614Ala ABCC6 p.His632Gln ABCC6 p.Arg419Gln ABCC6 p.Glu422Lys ABCC6 p.Glu1427Lys ABCC6 p.Ser587Cys ABCC6 p.Ala950Val ABCC6 p.Asn428Ser Exon Mutation AS Control Decision Wild/Wild Wild/Mut Mut/Mut Wild/Wild Wild/Mut Mut/Mut Undetermine 10 c.1256G>A (p.R419Q) 45 3 6 150 0 0 0 * 10 c.1264G>A (p.E422K) 53 1 0 150 0 0 0 * 10 c.1283A>G (p.N428S) 54 0 0 148 2 0 0 # 10 c.1312G>A (p.V438M) 54 0 0 149 1 0 0 # 13 c.1760C>G (p.S587C) 53 1 0 149 1 0 0 # 14 c.1841T>C (p.V614A) 40 12 2 89 56 5 0 $ 15 c.1896C>A (p.H632Q) 30 15 9 90 55 5 0 $ 19 c.2542delG 34 13 7 149 1 0 0 * 22 c.2849C>T (p.A950V) 53 1 0 149 1 0 0 # 23 Del_Exon23 52 0 2 150 0 0 0 * 27 c.3803G>A (p.R1268Q) 29 16 9 105 42 3 0 $ 27 c.3774-3775insertC 53 1 0 147 0 0 3 * 30 c.4279G>A (p.E1427K) 53 1 0 150 0 0 0 * For ABCC6 proteins, the designations for the mutations refer to the position of the amino acid substitution, where amino acid terminus. Nonsynonymous variants were shown by the amino acid numbers started by the strat codon methionine. The cDNA base numbers refer to the nucleotide in the cDNA, where nucleotide 1 is the A of the first ATG. * Causal mutation definitely. Login to comment