ABCMdb

PMID: 25342496

Kubitz R, Droge C, Kluge S, Stross C, Walter N, Keitel V, Haussinger D, Stindt J
Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis.
Clin Rev Allergy Immunol. 2015 Jun;48(2-3):273-84. doi: 10.1007/s12016-014-8457-4., [PubMed]

Sentences

No. Mutations Sentence Comment

50 ABCB11 p.Glu297Gly It has been shown that, BSEP with the common PFIC-2-related mutation E297G is trapped in the ER in a core-glycosylated state [29]. Login to comment 51 ABCB11 p.Val444Ala ABCB11 p.Gly982Arg ABCB11 p.Tyr818Phe The three mutations/variants Y818F, G982R, and V444A have been found on the same allele in a PFIC-2 patient. Login to comment 52 ABCB11 p.Gly982Arg ABCB11 p.Tyr818Phe BSEP with Y818F together with G982R is poorly expressed. Login to comment 53 ABCB11 p.Val444Ala The combination with the common BSEP polymorphism V444A results in complete degradation by ERAD, which can only be unmasked by proteasomal inhibition [22]. Login to comment 87 ABCB11 p.Gly982Arg ABCB11 p.Gly982Arg ABCB11 p.Tyr818Phe ABCB11 p.Arg303Gly ABCB11 p.Leu581Phe Sex Age at LTX (years) Zygosity Nucleotide change Predicted (protein) effect BSEP expression (before LTX) BSEP autoantibodies detected Symptom recurrence- time after LTX (years) Triggering factors 1 [22, 63] F 3.5/3.5/4.9 hom hom c.2453A>T c.2944G>A p.Y818F p.G982R Absent (exp) Yes 1/0.4 Graft rejection after first LTX 2 [23] M 5.2 hom c.907A>G p.R303G Absent Yes 12 Unknown 3 [23] F 3.7 com het c.1741C>T IVS12+1G>T a p.L581F abb splic Absent Yes 3.5/5.2/8.1/12.1/13 EBV infection; ࢑ corticosteroids 4 [23] F 2.2 hom IVS17+1T>A a abb splic Absent Yes 2.1/4 Low CsA, switch from Tac to CsA 5 [62, 63] F 9 com het c.301delCA c.2944G>A p.Q101Dfs8X p.G982R Absent NA 3.3/17 ࢑ IS, pregnancy? Login to comment 88 ABCB11 p.Val481Gln 6 [62] M 2.8 hom c.77-19T>A p.Y26Ifs7X Absent Yes (rBsep) 4.8 ࢑ IS 7 [63] - 2.4 hom c.908+1G>A abb splic Absent NA 0.8 Unknown 8 [63] - 3 com het c.1145_1165del c.2012-8T>G p.A382_388del abb splic Absent NA 3/8/8.6 Unknown 9 [63] - 1.8 com het c.1941delA c.2012-8T>G p.G648Vfs6X abb splic Absent NA 3.2/3.6 Unknown 10 [63] - 0.8 com het c.2783_2787dup5 c.1442T>A p.K930Efs79X p.V481Q Absent NA 1/1.4 Unknown 11 [61] M 0.8/3.5 hom c.2783_2787dup5 p.K930Efs79X Absent YES 1.7/5 Unknown 12 [61] M 5 hom c.1639-2A>C abb splic Absent YES 12 Unknown abb splic aberrant splicing predicted, com het compound heterozygous, CsA cyclosporin A, EBV Epstein-Barr virus, exp experimental, F female, hom homozygous, IS immunosuppression, IVS intervening sequence, M male, NA not assessed, Tac tacrolimus a Sequence position not precisely defined Milder forms of BSEP deficiency (especially BRIC-2 and ICP) often respond well to therapy with ursodeoxycholic acid (UDCA), whereas a substantial number of patients with a PFIC-2 phenotype do not benefit from UDCA at all. Login to comment 112 ABCB11 p.Asp482Gly ABCB11 p.Gly982Arg ABCB11 p.Arg1050Cys ABCB11 p.Gly374Ser Following this report, similar observations were published (1) K930Efs79X wtBSEP (2) (3) (4) R1050C (7) D482G G374S (6) (5) c.150+3A>C (8) G982R Fig. 2 Different effects of genetic ABCB11 variants on processing and function of BSEP. Login to comment 117 ABCB11 p.Gly374Ser Mutations such as G374S have no effects on expression but display impaired or absent transport activity (6). Login to comment