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2016, Number 5

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Ann Hepatol 2016; 15 (5)

Bile salt export pump deficiency disease: two novel, late onset, ABCB11 mutations identified by next generation sequencing

Vitale G, Pirillo M, Mantovani V, Marasco E, Aquilano A, Gamal N, Francalanci P, Conti F, Andreone P

Language: English
References: 26
Page: 795-800
PDF size: 193.50 Kb.


ABSTRACT

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive cholestatic diseases of childhood and represents the main indication for liver transplantation at this age; PFIC2 involves ABCB11 gene, that encodes the ATPdependent canalicular bile salt export pump (BSEP). Benign intrahepatic cholestasis (BRIC) identifies a group of diseases involving the same genes and characterized by intermittent attacks of cholestasis with no progression to liver cirrhosis. Diagnosis with standard sequencing techniques is expensive and available only at a few tertiary centers. We report the application of next generation sequencing (NGS) in the diagnosis of the familial intrahepatic cholestasis with a parallel sequencing of three causative genes. We identified the molecular defects in ABCB11 gene in two different probands who developed a severe cholestatic disease of unknown origin. In the first patient a compound heterozygosity for the novel frameshift mutation p.Ser1100GlnfsX38 and the missense variant p.Glu135Lys was detected. In the second patient, triggered by contraceptive therapy, we identified homozygosity for a novel missense variant p.Ala523Gly. In conclusion, these mutations seem to have a late onset and a less aggressive clinical impact, acting as an intermediate form between BRIC and PFIC.


REFERENCES

  1. Morotti RA, Suchy FJ, Magid MS. Progressive Familial Intrahepatic Cholestasis (PFIC) Type 1, 2, and 3: A Review of the Liver Pathology Findings. Seminars in Liver Disease 2011; 31: 3-10.

  2. Hori T, Nguyen JH, Uemoto S. Progressive familial intrahepatic cholestasis. Hepatobiliary Pancreat Dis Int 2010; 9: 570-8.

  3. Folvik G, Hilde O, Helge GO. Benign recurrent intrahepatic cholestasis: review and long-term follow-up of five cases. Scand J Gastroenterol 2012; 47: 482-8.

  4. Jacquemin E, Hermans D, Myara A, Habes D, Debray D, Hadchouel M, Sokal EM, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology 1997; 25: 519-23.

  5. Bustorff-Silva J, Sbraggia Neto L, Olímpio H, de Alcantara RV, Matsushima E, De Tommaso AM, Brandăo MA, et al. Partial internal biliary diversion through a cholecystojejunocolonic anastomosis - a novel surgical approach for patients with progressive familial intrahepatic cholestasis: a preliminary report. J Pediatr Surg 2007; 42: 1337-40.

  6. Stapelbroek JM, van Erpecum KJ, Klomp LW, Venneman NG, Schwartz TP, van Berge Henegouwen GP, et al. Nasobiliary drainage induces long-lasting remission in benign recurrent intrahepatic cholestasis. Hepatology 2006; 43: 51-3.

  7. Zellos A, Lykopoulou L, Polydorou A, Tanou K, Jirsa M, Roma E, Knisely AS. Nasobiliary drainage in an episode of intrahepatic cholestasis in a child with mild ABCB11 disease. J Pediatr Gastroenterol Nutr 2012; 55: 88-90.

  8. Soubrane O, Gauthier F, DeVictor D, Bernard O, Valayer J, Houssin D, Chapuis Y. Orthotopic liver transplantation for Byler disease. Transplantation 1990; 50: 804-6.

  9. Cutillo L, Najimi M, Smets F, Janssen M, Reding R, de Ville de Goyet J, Sokal EM. Safety of living-related liver transplantation for progressive familial intrahepatic cholestasis. Pediatr Transplant 2006; 10: 570-4.

  10. Naoi S, Hayashi H, Inoue T, Tanikawa K, Igarashi K, Nagasaka H, Kage M, et al. Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2. J Pediatr 2014; 164: 1219-27.

  11. Gonzales E, Grosse B, Cassio D, Davit-Spraul A, Fabre M, Jacquemin E. Successful mutation-specific chaperone therapy with 4-phenylbutyrate in a child with progressive familial intrahepatic cholestasis type 2. J Hepatol 2012; 57: 695-8.

  12. Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology 2011; 53: 1377-87.

  13. Strautnieks SS, Byrne JA, Pawlikowska L, Cebecauerová D, Rayner A, Dutton L, Meier Y, et al. Severe Bile Salt Export Pump Deficiency: 82 Different ABCB11 Mutations in 109 Families. Gastroenterology 2008; 134: 1203-14.

  14. Degiorgio D, Colombo C, Seia M, Porcaro L, Costantino L, Zazzeron L, Bordo D, et al. Molecular Characterization and Structural Implications of 25 New ABCB4 Mutations in Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3). EJHG 2008; 15: 1230-8.

  15. Klomp LWJ, Vargas JC, van Mil SWC, Pawlikowska L, Strautnieks SS, van Eijk MJT, Juijn JA, et al. Characterization of Mutations in ATP8B1 Associated with Hereditary Cholestasis. Hepatology 2004; 40: 27-38.

  16. Xuan J, Yu Y, Qing T, Guo L, Shi L. Next-generation sequencing in the clinic: promises and challenges. Cancer Lett 2013; 340: 284-95.

  17. Sambrotta M, Strautnieks S, Papouli E, Rushton P, Clark BE, Parry DA, Logan CV, et al. Mutations in TJP2 cause progressive cholestatic liver disease. Nat Genet 2014; 46: 326-8.

  18. Herbst SM, Schirmer S, Posovszky C, Jochum F, Rödl T, Schroeder JA, Barth TF, et al. Taking the next step forward - Diagnosing inherited infantile cholestatic disorders with next generation sequencing. Mol Cell Probes 2015 Mar 13. doi: 10.1016/j.mcp.2015.03.001.

  19. van Ooteghem NA, Klomp LW, van Berge-Henegouwen GP, Houwen RH. Benign recurrent intrahepatic cholestasis progressing to progressive familial intrahepatic cholestasis: low GGT cholestasis is a clinical continuum. J Hepatol 2002; 36: 439-43.

  20. Lam CW, Cheung KM, Tsui MS, Yan MS, Lee CY, Tong SF. A patient with novel ABCB11 gene mutations with phenotypic transition between BRIC2 and PFIC2. J Hepatol 2006; 44: 240-2.

  21. Stindt J, Ellinger P, Weissenberger K, Dröge C, Herebian D, Mayatepek E, Homey B, et al. A novel mutation within a transmembrane helix of the bile salt export pump (BSEP, ABCB11) with delayed development of cirrhosis. Liver Int 2013; 33: 1527-35.

  22. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, et al. A Method and Server for Predicting Damaging Missense Mutations. Nature Methods 2010; 7: 248-9.

  23. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009; 4: 1073-8.

  24. Schwarz JM, Cooper DN, Schuelke M, Seelow D. Mutation- Taster2: Mutation Prediction for the Deep-Sequencing Age. Nature Methods 2014; 11: 361-2.

  25. Anzivino C, Odoardi MR, Meschiari E, Baldelli E, Facchinetti F, Neri I, Ruggiero G, et al. ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population. Dig Liver Dis 2013; 45: 226-32.

  26. Byrne JA, Strautnieks SS, Ihrke G, Pagani F, Knisely AS, Linton KJ, Mieli-Vergani G, et al. Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology 2009; 49: 553-67.




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