ABCMdb

PMID: 19845854

Liu LY, Wang ZL, Wang XH, Zhu QR, Wang JS
ABCB11 gene mutations in Chinese children with progressive intrahepatic cholestasis and low gamma glutamyltransferase.
Liver Int. 2010 Jul;30(6):809-15. Epub 2009 Oct 21., [PubMed]

Sentences

No. Mutations Sentence Comment

52 ABCB11 p.Gln869Pro ABCB11 p.Gly499Glu The exons in which G499E, Q869P or A535A located had been sequenced in 50 children with nonprogressive intrahepatic cholestasis and elevated GGT levels, and no changes were found in these sites (unpublished data). Login to comment 54 ABCB11 p.Gly499Glu ABCB11 p.Ala167Thr ABCB11 p.Cys107Arg ESE Finder showed that missense mutation 319T 4C (C107R) induced the introduction of a splicing factor at the SRp55 binding site; 499G 4 A (A167T) resulted in an enhanced SF2/ASF binding site (score 2.60677 vs. 3.05400); and 1496G 4 A (G499E) led to a branch site appearing in exon 14. Login to comment 55 ABCB11 p.Gln869Pro ABCB11 p.Ala167Thr ABCB11 p.Gly1292Val The Splice Site Prediction by Neural Network program showed that a new cryptic acceptor splice site appeared when 499G 4 A (A167T) in exon seven occurred, so did the mutation 3875G 4 T (G1292V) in exon 28; 2606A 4G (Q869P) introduced a new cryptic donor splice site in exon 21. Login to comment 65 ABCB11 p.Ala167Thr Case 2 with homozygous mutations 499G 4 A (A167T) had a liver wedge biopsy when he had an operation for gallstone at 2.5 years old in another hospital, and his pathology records did not describe whether giant cell transformation of hepatocytes had appeared in his liver histology. Login to comment 73 ABCB11 p.Gln869Pro ABCB11 p.Gln869Pro ABCB11 p.Gly499Glu ABCB11 p.Cys107Arg ABCB11 p.Gly1292Val ABCB11 p.Arg415* ABCB11 p.Gly188Trp ABCB11 p.Gln1058* Ageat onset/sexSymptoms Ageat follow-upOutcomePathologicalfeaturesNucleotidechangeDeducedeffectMutationorigin 23d/MPersistentjaundice, pruritus,gallstone 6yAliveHepatocellularcholestasis, portalfibrosis Homozygous499G4AHomozygousA167TBothparentswerecarriers 350d/FPersistentjaundice, hepaticfailure 9mDeathNAHeterozygous2104C4THeterozygousQ702XNA 52d/MJaundice,pruritus5yLostfollow-upHepatocellularcholestasis, giantcelltransformation, portalfibrosis Compoundheterozygous 562G4T/IVS2213A4G/ IVS4-74A4T Compoundheterozygous G188W/splicingdefect NA 113m/FPersistentjaundice, pruritus 1.5yAliveHepatocellularcholestasis, giantcelltransformation Compoundheterozygous 1496G4A/2606A4C Compoundheterozygous G499E/Q869P G499Ewaspaternal,Q869P wasmaternal 142m/MJaundice,failureto thrive 14mLostfollowupNACompoundheterozygous 1605C4TÃ/IVS25-6C4G Compoundheterozygous A535AÃ/splicingdefect A535Awasmaternal, IVS25-6C4Gwaspaternal 15Birth/MProgressivejaundice, pruritus 2.5yLostfollow-upCholestasis,giantcell transformation,portal fibrosis Compoundheterozygous 319T4C/3172C4T Compoundheterozygous C107R/Q1058X C107Rwasmaternal, Q1058Xwaspaternal 20Birth/MProgressivejaundice15mLostfollow-upCholestasis,giantcell transformation,early cirrhosis Compoundheterozygous 1243C4T/3875G4T Compoundheterozygous R415X/G1292V R415Xwaspaternal, G1292Vwasmaternal Ã1605C4T(A535A):anuncommonSNP,reducingthelevelsofBSEPexpression(19). Login to comment 79 ABCB11 p.Gly499Glu ABCB11 p.Gly1292Val G499E and G1292V occur in two highly conserved nucleotide-binding fold (NBF) domains (residues 414-610, 1072-1321) (21). Login to comment 87 ABCB11 p.Arg303Lys All of them, except for R303K, were different from those reported in other population groups. Login to comment 89 ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly Common mutations, such as E297G and D482G detected in western population (23), were not found in Chinese, either from Taiwan (9, 10) or from mainland China. Login to comment 92 ABCB11 p.Arg415* ABCB11 p.Gln1058* ABCB11 p.Gln702* Three nonsense mutations were detected in the study: R415X, Q702X and Q1058X. Login to comment 93 ABCB11 p.Gln702* Q702X is the first identified mutation in exon 18 of ABCB11 (Fig. 2). Login to comment 119 ABCB11 p.Arg303Lys R303K found in Central Asian, Arab and Taiwan Chinese is shown in green. Login to comment 121 ABCB11 p.Ala167Thr Mutation 499G 4 A (A167T) occurs in the transmembrane domain. Login to comment 124 ABCB11 p.Ala167Thr The A167T mutation introduces a hydrophilic residue into the hydrophobic domain. Login to comment 130 ABCB11 p.Met183Val ABCB11 p.Gly188Trp 562G 4 T (G188W) is in the vicinity of the mutations 547A 4G (M183V) that was detected in a Taiwan Chinese with PFIC2 (10). Login to comment 131 ABCB11 p.Ala167Thr These two mutations and the above-mentioned mutation A167T in the first transmembrane domain were all in exon 7. Login to comment 133 ABCB11 p.Thr859Arg ABCB11 p.Gln869Pro Missense mutation 2606A 4G (Q869P) is located in the fourth intracellular loop and in the vicinity of the mutation T859R detected in a European patient (23). Login to comment 134 ABCB11 p.Gln869Pro As the nucleotide changes, 2606A 4G (Q869P) introduces a new cryptic donor splice site appearing. Login to comment 135 ABCB11 p.Gly499Glu ABCB11 p.Gly1292Val 1496G 4 A (G499E) and 3875G 4 T (G1292V) are in two highly conserved nucleotide-binding fold (NBF) domains (residues 414-610, 1072-1321) (21). Login to comment 137 ABCB11 p.Gly499Glu In addition, 1496G 4 A (G499E) leads to a de novo branch site in exon 14, which may result in mRNA splicing in abnormal site. Login to comment 138 ABCB11 p.Gly1292Val 3875G 4 T (G1292V) introduces a new cryptic donor splice site in exon 28, which may affect mRNA splicing. Login to comment