ABCB11 p.Val481Gln
| Reviews: |
p.Val481Glu
D
|
| Predicted by SNAP2: | A: D (66%), C: N (61%), D: D (80%), E: D (80%), F: D (53%), G: D (75%), H: D (75%), I: N (97%), K: D (80%), L: N (97%), M: N (53%), N: D (75%), P: D (80%), Q: D (75%), R: D (71%), S: D (66%), T: D (66%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Autoimmune BSEP disease: disease recurrence after ... Clin Rev Allergy Immunol. 2015 Jun;48(2-3):273-84. doi: 10.1007/s12016-014-8457-4. 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., [PMID:25342496]
Abstract [show]
Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10 % of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this "new" disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of "autoimmune BSEP disease."
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No. Sentence Comment
88 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.
X
ABCB11 p.Val481Gln 25342496:88:384
status: NEW