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| 1 | Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation显示文摘AIM To investigate the relation of two different mutations to the outcome of partial external biliary diversion(PEBD)in severe bile salt export pump(BSEP) deficiency.METHODS Mutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney(HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatographytandem mass spectrometry. Wild-type and mutant BSEP transport of [~3H]-labeled taurocholate(TC) and taurochenodeoxycholate(TCDC) was assessed by vesicular transport assays.RESULTS A girl(at 2 mo) presented with pruritus, jaundice and elevated serum bile salts(BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919 del and the nonsense mutation p.R1235 X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy(age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032 R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives(< 5%). The patients' native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919 del and p.G1032 R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively.CONCLUSION In summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2(PFIC-2). | Philipp Ellinger Jan Stindt Carola Droge Katharina Sattler Claudia Stross Stefanie Kluge Diran Herebian Sander HJ Smits Martin Burdelski Sebastian Schulz-Jürgensen Antje Ballauff Jan Schulte am Esch Ertan Mayatepek Dieter Haussinger Ralf Kubitz Lutz Schmitt | 2017 | World Journal of Gastroenterology2017，23，29： | 4 |
| 2 | LDL-Apheresis for the treatment of hyperchylomicronemia-induced pancreatitis 显示文摘 | Sattler AM Boek K Schmidt S | 2003 | Z Kardiol2003，92，3： | 1 |
| 3 | Increased osteoprote- gerin serum levels in men with coronary artery disease 显示文摘 | Schoppet M Sattler AM Schaefer JR | 2003 | J Clin Endocrinol Metab2003，88，3： | 1 |
| 4 | Novel aspects on RANK ligand and osteoprotegerin in osteoporosis and vascular dis- ease显示文摘 | Sattler AM Schoppet M Schaefer 1R | 2004 | CalcifTissue Int2004，74，1： | 1 |
| 5 | Increased osteoprotegerin serum levels in men with coronary artery disease显示文摘 | Schoppet M Sattler AM Schaefer JR | | 0，，： | 1 |
| 6 | Excessive hyperchylomicronemia - a rare cause of acute retrosternal and epigastric pain in pregnancy显示文摘 | Sattler AM Bock K Schmidt S | 2003 | Herz2003，28，3： | 1 |
| 7 | Increased oste- oprotegerin serum levels in men with coronary artery disease 显示文摘 | Schoppet M Sattler AM Juergen R | 2003 | Clin Endocrinol Metab2003，88，3： | 1 |
| 8 | Osteoprotegerin gene poly?morphisms in men with coronary artery disease显示文摘 | Soufi M Schoppet M Sattler AM | 2004 | J Clin Endocri?nol Metab2004，89，8： | 1 |
| 9 | Increased osteoprotegerin serum levels in men with coronary artery disease显示文摘 | Schoppet M Sattler AM Schaefer JR | 2003 | J Clin Endocrinol Metab2003，88，3： | 1 |
| 10 | Osteoprotegerin gene polymorphisms in men with coronary artery disease 显示文摘 | Soufi M Schoppet M Sattler AM etal | 2004 | ClinEndocrinolMetah2004，89，8： | 1 |
| 11 | Osteopretegerin gene polymorphism in men with coronary artery disease显示文摘 | Soufi M Schoppet M Sattler AM | 2004 | J Clin Endocrinol Metab2004，89，8： | 1 |
| 12 | Increased osteoprotegerin serum levels in men with coronary artery disease显示文摘 | Schoppet M Sattler AM Juergen R | | 0，，88： | 1 |
| 13 | Osteoprotegerin gene polymorphisms in men with coronary artery disease显示文摘 | Soufi M Schoppet M Sattler AM | | 0，，08： | 1 |
| 14 | Osteoprotegeringene polymorphisms in men with coronary artery disease显示文摘 | Soufi M Schoppet M Sattler AM | 2004 | J Clin Endocrinol Metab2004，89，8： | 1 |
| 15 | Osteoprotegerin genepolymorphisms in men with coronary artery disease 显示文摘 | Soufi M Schoppet M Sattler AM | 2004 | J ClinEndocrinol Metab2004，89，： | 1 |
| 16 | Osteoprotegeringene polymorphisms in men with coronary artelT disease显示文摘 | Soufi M Schoppet M Sattler AM | 2004 | J Ciin Endocrinol Metab2004，89，8： | 1 |
| 17 | El Salvadorearthquakes:Relationships among acute stress disorder symp-toms,depression,traumatic event exposure,and resource coss显示文摘 | Sattler DN Alvarado AM Castro NB | 2006 | J Traumat Stress2006，19，6： | 1 |
| 18 | Increased osteoprotegerin serum levels in men with coronary artery disease显示文摘 | Schoppet M Sattler AM Schaefer JR | | 0，，89： | 1 |
| 19 | Osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in atherosclerosis显示文摘 | Schoppet M Sattler AM Schaefer JR | 2006 | Atherosclerosis2006，184，2： | 1 |
| 20 | Increased osteoprotegerin serum levels in men with coronary artery disease显示文摘 | Schoppet M Sattler AM Schaefer JR | 2003 | J Clin Endocrinol Metab2003，88，3： | 1 |
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