ABCMdb

PMID: 22343912

Fang LJ, Wang XH, Knisely AS, Yu H, Lu Y, Liu LY, Wang JS
Chinese children with chronic intrahepatic cholestasis and high gamma-glutamyl transpeptidase: clinical features and association with ABCB4 mutations.
J Pediatr Gastroenterol Nutr. 2012 Aug;55(2):150-6., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCB4 p.Asp459Gly ABCB4 p.Arg47* ABCB4 p.Arg582Gln Apart from c.139C>T (p.R47X), all were novel, including c.344þ2_þ3insT, c.1376A>G (p.D459G), c.1745G>A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308). Login to comment 76 ABCB4 p.Asp459Gly ABCB4 p.Arg47* ABCB4 p.Arg582Gln Apart from c.139C>T (p.R47X) (19), they were novel; they included c.344þ2_þ3insT, c.1376A>G (p.D459G), c.1745G>A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308). Login to comment 79 ABCB4 p.Arg47* Translation would generate a truncated protein (p.R47X) including only the first intracellular domain. Login to comment 83 ABCB4 p.Asp459Gly ABCB4 p.Arg582Gln Amino acid residues in the first highly conserved nucleotide-binding domains (NBDs) (residues 404-630) are affected by c.1376A>G (p.D459G) and c.1745G>A (p.R582Q). Login to comment 87 ABCB4 p.Asp459Gly ABCB4 p.Arg582Gln The absolute differences between the 2 profile score sets are 1.988 and 2.468, respectively, indicating that c.1376A>G (p.D459G) is likely to affect protein function and that c.1745G>A (p.R582Q) is able to affect protein function. Login to comment 88 ABCB4 p.Asp459Gly ABCB4 p.Arg582Gln ESE Finder predicted c.1376A>G (p.D459G) to decrease the splicing-factor score at a SF (splicing factor)2/alternative splicing factor (ASF)-binding site (from 3.960444 to 3.233662) and to abolish a SC35-binding site; it predicted c.1745G>A (p.R582Q) to enhance the splicing-factor score at a SF2/ASF-binding site (from 3.317899 to 3.765121), to abolish a SF2/ASF-binding site, and to generate a new SRp40-binding site. Login to comment 92 ABCB4 p.Arg47* ABCB4 p.Arg582Gln MDR3 staining was completely absent with compound heterozygous mutations c.139C>T (p.R47X) and c.1745G>A (p.R582Q) (case 13, Fig. 1E). Login to comment 93 ABCB4 p.Asp459Gly Faint MDR3 staining was found with compound heterozygous mutations c.1376A>G (p.D459G) and M1276WfsX1308 (case 11, Fig. 1G). Login to comment 144 ABCB4 p.Arg47* ABCB4 p.Arg582Gln Normal MDR3 staining (A) and normal BSEP staining (B) in control liver specimen; normal MDR3 staining (C) and normal BSEP staining (D) in case 6 without ABCB4 mutation; absence of MDR3 staining (E) and normal BSEP staining (F) in case 13 with compound heterozygous ABCB4 mutations c.139C>T (p.R47X) and c.1745G>A (p.R582Q); faint MDR3 staining (G) and normal BSEP staining (H) in case 11 with compound heterozygous ABCB4 mutations c. Login to comment 145 ABCB4 p.Asp459Gly 3825_3826delA (p.M1276WfsX1308) and c.1376A>G (p.D459G). Login to comment