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P13.14 Liver Transplantation in Alagille Syndrome with NOTCH2 genetic variant. Case Report

Luciola Vasquez, Peru

pediatrician - nephrologist pediatrician
Organ Transplant Department
Guillermo Almenara Irigoyen Hospital.


Liver transplantation in alagille syndrome with NOTCH2 genetic variant: case report

Luciola Vasquez1, Bertha Cárdenas1, Martín Padilla1, Carlos Rondón1.

1Department of Organ Transplantation, Guillermo Almenara Irigoyen National Hospital, Lima, Peru

Introduction: Alagille-Watson Syndrome, an autosomal dominant multiorgan disease, with a frequency of 1/30000; presents an alteration in the NOTCH receptor pathway, considering the transmembrane proteins: JAGGED1 (JAG1) and NOTCH2 the affected ones. The study of chromosome 20 (short arm) has been able to identify variants in this pathway, reporting mostly alterations in the JAGGED1 ligand and between 2-4% in the NOTCH2 receptor. The genetic alteration in the NOTCH2 receptor is less clear, being the majority missense type, so that cardiac characteristics, vertebral alterations and facial features are expressed with less prevalence.

Method: Case Report.

Results: Female patient who presented jaundice since she was 3 months old.  At 7 months she underwent a surgical biopsy, with findings: hypotrophic gallbladder, no extrahepatic biliary tract was observed. Liver biopsy: ductular proliferation in all portal spaces; cholestasis in hepatocytes, canaliculi and ducts; slightly active micronodular cirrhosis with ductopenia. Laboratory: urea creatinine dissociation, hypertriglyceridemia; with parameters in ranges of malnutrition. At 18 months of age, being considered a ductopenic syndrome, she was sent abroad to undergo liver transplantation with a living donor (Hospital Universitario Austral-Argentina). Upon return to our center and during the follow up, a genetic study was performed in which the NOTCH2 gene was reported, with the variant c.4316G>A (p.Cys1439Tyr), heterozygous, of uncertain significance; this variant presents a substitution of Cysteine for Tyrosine in codon 1439 of the NOTCH2 protein (p.Cys1439Tyr) (Invitae #: RQ2577430; Invitae Corporation, San Francisco, CA 94103).

Conclusion: With the identification of this gene the patient has a definitive diagnosis of Alagille syndrome with NOTCH2 gene involvement with an uncommon, rare variant (p.Cys1439Tyr).


  1. Tobias M. Ballhause et al. Review Relevance of Notch Signaling for Bone Metabolism and Regeneration. Int. J. Mol. Sci. 2021, 22, 1325.
  2. Mohammed D. Ayoub 1,2 and Binita M. Kamath. Review Alagille Syndrome:  Diagnostic Challenges and Advances in ManagementDiagnostics 2020, 10, 90.7.doi:10.3390/diagnostics10110907.
  3. Melissa A. Gilbert et al. Alagille syndrome mutation update: Comprehensive overview of JAG1 and NOTCH2 of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification. Human Mutation. 2019;40:2197-2220.
  4. Melissa A. Gilbert, PhD and Nancy B. Spinner, PhD. Spinner, PhD. Alagille syndrome: Genetics and Functional Models Functional Models. Curr Pathobiol Rep. 2017 September ; 5(3): 233- 241. doi:10.1007/s40139-017-0144-8.

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