ABCMdb

PMID: 19261551

Tavian D, Degiorgio D, Roncaglia N, Vergani P, Cameroni I, Colombo R, Coviello DA
A new splicing site mutation of the ABCB4 gene in intrahepatic cholestasis of pregnancy with raised serum gamma-GT.
Dig Liver Dis. 2009 Sep;41(9):671-5. Epub 2009 Mar 3., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCB4 p.Arg590Gln We identified also one already described p.R590Q mutation in a woman who had significantly higher serum levels of alkaline phosphatase, aspartate, and alanine aminotransferase. Login to comment 67 ABCB4 p.Arg590Gln ABCB4 p.Arg652Gly Patients Involved regions Nucleotide positiona Reference nucleotide Nucleotide variant Effect on proteinb GenBank accession numberc 9d Promoter c.-495 C G 3, 9 Promoter c.-378 T C 2 Exon 4 c.175 C T p.L59L 2, 3, 4, 5d , 7, 9, 10 Exon 6 c.504 T C p.N168N 9 Intron 7 c.709-2 A G p.I237VfsX250 EU142941 2, 7 Exon 8 c.711 A T p.I237I 2, 7 Intron 8 c.834-66 G T 7 Intron 11 c.1231-81 T delT 2 Exon 15 c.1769 G A p.R590Q 7 Exon 16 c.1954 A G p.R652G 7 Intron 16 c.2064+55 A G 2 Intron 17 c.2211+16 T C 7 Intron 20 c.2478+40 A G 7 Intron 20 c.2479-67 G delG 7 Intron 21 c.2682+22 T C EU142942 7 Intron 21 c.2683-197 T C 7 Intron 27 c.3655-72 T C In bold the two mutations which were most likely to cause an impairment of about 50% of the ABCB4 floppase activity in ICP patients n. 2 and n. 9. a Nucleotide A of the ATG of the initiator Met codon is position +1 of cDNA sequence (reference sequence GenBank NM 018849); b The protein GenBank reference number is NP 061337. c GenBank accession number of the new sequences identified in this study. Login to comment 94 ABCB4 p.Arg590Gln The second mutation is the missense p.R590Q, detected in the heterozygous state of the ICP patient n. 2 (ICP2), who presented with occasional pruritus, significantly higher serum levels of alkaline phosphatase, aspartate, and alanine aminotransferase (Table 1). Login to comment 95 ABCB4 p.Arg590Gln ABCB4 p.Arg590Gln The p.R590Q mutation is located in the nucleotide binding domain 1 (NBD1) of the ABCB4 protein and was not present in any of the 43 control women. Login to comment 96 ABCB4 p.Arg590Gln The p.R590Q mutation is located in the nucleotide binding domain 1 (NBD1) of the ABCB4 protein and was not present in any of the 43 control women. Login to comment 113 ABCB4 p.Arg590Gln The mutation is localized in exon 15 and causes significant changes, with respect to polarity (p.R590Q) in the very well conserved NBD1 region of the protein. Login to comment 114 ABCB4 p.Arg590Gln The mutation is localized in exon 15 and causes significant changes, with respect to polarity (p.R590Q) in the very well conserved NBD1 region of the protein. Login to comment 116 ABCB4 p.Arg590Gln Furthermore, in our previous detailed molecular ABCB4 analysis of children with PFIC3 phenotype [13], the p.R590Q has been ascribed to the mutation responsible for substantial impairment of ABCB4 floppase activity. Login to comment 117 ABCB4 p.Arg590Gln Furthermore, in our previous detailed molecular ABCB4 analysis of children with PFIC3 phenotype [13], the p.R590Q has been ascribed to the mutation responsible for substantial impairment of ABCB4 floppase activity. Login to comment