Phenotypic Divergence of JAG1-and NOTCH2-Associated Alagille Syndrome & Disease-Specific NOTCH2 Variant Classification Guidelines

Por: Vandriel SM, Li LT, She H, Wang JS, Loomes KM, Piccoli DA, Jankowska I, Czubkowski P, Gliwicz-Miedzinska D, D'Antiga L, Nicastro E, Lacaille F, Debray D, Sokal ÉM, Demaret T, Fawaz RL, Nastasio S, Kim KM, Oh SH, Fischler B, Arnell H, Larson-Nath C, Hardikar W, Shankar S, Sundaram SS, Chaidez A, Bulut P, Calvo PL, Kasahara M, Blondet N, Lurz E, Kavallar AM, Gonzales EM, Jacquemin E, Bouligand J, Ebel NH, Feinstein JA, Siew SM, Stormon MO, Karpen SJ, Romero R, Jensen MK, Jaramillo C, Squires JE, Bedoyan SM, Kelly DA, Hartley J, Verkade HJ, Lee WS, Lertudomphonwanit C, Fischer RT, Lin HC, Rock N, Mozer-Glassberg Y, Roberts AJ, Evans HM, Karnsakul W, Nebbia G, Wolters VM, Valentino PL, Bernabeu JQ, Aqul AA, Arikan C, Tamara ML, Molera C, Sandahl TD, Indolfi G, Zizzo AN, Zellos A, Quiros-Tejeira RE, Santos-Silva E, Schwarz KB, Brecelj J, Sanchez MC, Cavalieri ML, Tzivinikos C, Wiecek S, Eshun J, Kerkar N, Mujawar Q, Önal Z, Gonçalves C, Garcia J, Alam S, Jimenez-Rivera C, Bujanda L, Thompson RJ, Hansen BE, Spinner NB, Gilbert MA and Kamath BM

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Publicada: 1 sep 2025

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Filiaciones:
Vandriel SM:
 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Canada

Li LT:
 The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China

She H:
 The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China

Wang JS:
 The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China

Loomes KM:
 Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

Piccoli DA:
 Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

Jankowska I:
 Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland

Czubkowski P:
 Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland

Gliwicz-Miedzinska D:
 Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland

D'Antiga L:
 Pediatric Hepatology, Gastroenterology and Transplantation, Ospedale Papa Giovanni XXIII, Bergamo, Italy

 Department of Medicine and Surgery, University of Milano - Bicocca, Milan, Italy

Nicastro E:
 Pediatric Hepatology, Gastroenterology and Transplantation, Ospedale Papa Giovanni XXIII, Bergamo, Italy

Lacaille F:
 Pediatric Gastroenterology-Nutrition and Hepatology Units, Necker-Enfants Malades Hospital, University of Paris, Paris, France

Debray D:
 Pediatric Liver Unit, National Reference Centre for Rare Pediatric Liver Diseases (Biliary Atresia and Genetic Cholestasis), FILFOIE, ERN RARE LIVER, Necker-Enfants Malades Hospital, University of Paris, Paris, France

Sokal ÉM:
 Service de Gastroentérologie & Hépatologie Pédiatrique, Cliniques Universitaires Saint-Luc, Brussels, Belgium

Demaret T:
 Service de Gastroentérologie & Hépatologie Pédiatrique, Cliniques Universitaires Saint-Luc, Brussels, Belgium

Fawaz RL:
 Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA

Nastasio S:
 Division of Gastroenterology, Hepatology, & Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA

Kim KM:
 Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea

Oh SH:
 Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea

Fischler B:
 Department of Paediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden

 CLINTEC, Karolinska Institutet, ERN Rare Liver, Stockholm, Sweden

Arnell H:
 Department of Paediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden

 Department of Women's and Children's Health, Karolinska Institutet, ERN Rare Liver, Stockholm, Sweden

Larson-Nath C:
 Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA

Hardikar W:
 Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne, Australia

Shankar S:
 Mazumdar Shaw Medical Center, Narayana Health, Bangalore, India

Sundaram SS:
 Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA

Chaidez A:
 Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA

Bulut P:
 Division of Pediatric Gastroenterology and Hepatology, Phoenix Children's Hospital, Phoenix, Arizona, USA

Calvo PL:
 Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Citta' della Salute e della Scienza, Turin, Italy

Kasahara M:
 Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan

Blondet N:
 Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, Washington, USA

Lurz E:
 Department of Pediatrics, LMU Munich, Dr. von Hauner Children's Hospital, University Hospital, Munich, Germany

Kavallar AM:
 Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria

Gonzales EM:
 Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Rare Pediatric Liver Diseases, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, AP-HP, University of Paris-Saclay, Le Kremlin-Bicêtre, France

 Inserm U1193, Hepatinov, University of Paris-Saclay, Orsay, France

Jacquemin E:
 Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Rare Pediatric Liver Diseases, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, AP-HP, University of Paris-Saclay, Le Kremlin-Bicêtre, France

 Inserm U1193, Hepatinov, University of Paris-Saclay, Orsay, France

Bouligand J:
 Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Le Kremlin-Bicêtre, France

Ebel NH:
 Division of Gastroenterology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA

Feinstein JA:
 Department of Pediatrics (Cardiology), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, California, USA

Siew SM:
 Department of Gastroenterology, The Children's Hospital at Westmead, Sydney, Australia

Stormon MO:
 Department of Gastroenterology, The Children's Hospital at Westmead, Sydney, Australia

Karpen SJ:
 Division of Pediatric Gastroenterology, Hepatology & Nutrition, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, Georgia, USA

 Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, Richmond, Virginia, USA

Romero R:
 Division of Pediatric Gastroenterology, Hepatology & Nutrition, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, Georgia, USA

Jensen MK:
 Division of Pediatric Gastroenterology, Hepatology and Nutrition, Primary Children's Hospital, University of Utah, Salt Lake City, Utah, USA

Jaramillo C:
 Division of Pediatric Gastroenterology, Hepatology and Nutrition, Primary Children's Hospital, University of Utah, Salt Lake City, Utah, USA

Squires JE:
 Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Bedoyan SM:
 Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Kelly DA:
 Liver Unit, Birmingham Women's & Children's Hospital NHS Trust, University of Birmingham, Birmingham, UK

Hartley J:
 Liver Unit, Birmingham Women's & Children's Hospital NHS Trust, University of Birmingham, Birmingham, UK

Verkade HJ:
 Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Lee WS:
 Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Lertudomphonwanit C:
 Division of Gastroenterology, Department of Pediatrics, Ramathibodi Hospital Mahidol University, Bangkok, Thailand

Fischer RT:
 Section of Hepatology, Department of Gastroenterology, Children's Mercy Kansas City, Kansas City, Missouri, USA

Lin HC:
 Division of Pediatric Gastroenterology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA

Rock N:
 Division of Pediatric Specialties, Department of Pediatrics, Gynecology, and Obstetrics, Swiss Pediatric Liver Center, University Hospitals Geneva, University of Geneva, Geneva, Switzerland

Mozer-Glassberg Y:
 Schneider Children's Medical Center of Israel, Institute of Gastroenterology, Nutrition and Liver Diseases, Petah Tikva, Israel

Roberts AJ:
 Department of Paediatric Gastroenterology, Starship Child Health, Auckland, New Zealand

Evans HM:
 Department of Paediatric Gastroenterology, Starship Child Health, Auckland, New Zealand

Karnsakul W:
 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Nebbia G:
 Servizio di Epatologia Pediatrica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Wolters VM:
 Department of Pediatric Gastroenterology, University Medical Centre Utrecht, Utrecht, the Netherlands

Valentino PL:
 Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, Washington, USA

Bernabeu JQ:
 Pediatric Hepatology and Liver Transplant Department, Hospital Universiatri Vall d'Hebron, Barcelona, Spain

 European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza, Italy

 European Reference Network on Transplantation in Children (ERN-TransplantChild), La Paz Institute of Biomedical Research, Hospital Universitario La Paz, Madrid, Spain

Aqul AA:
 University of Texas Southwestern Medical Centre in Dallas and Children's Health, Dallas, Texas, USA

Arikan C:
 Department of Pediatric Gastroenterology and Organ Transplant, Koc University School of Medicine, Istanbul, Turkey

Tamara ML:
 Paediatric Gastroenterology Unit, Cruces University Hospital, Bilbao, Spain

Molera C:
 Pediatric Gastroenterology Hepatology and Nutrition Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain

Sandahl TD:
 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark

Indolfi G:
 Meyer Children's Hospital IRCCS, Florence, Italy

Zizzo AN:
 Division of Paediatric Gastroenterology and Hepatology, London Health Sciences Centre, Children's Hospital, Western University, London, Ontario, Canada

Zellos A:
 Mitera Children's Hospital, Athens, Greece

Quiros-Tejeira RE:
 Department of Pediatrics, Children's Nebraska and University of Nebraska Medical Center, Omaha, Nebraska, USA

Santos-Silva E:
 Centro Materno-Infantil do Norte Albino Aroso, Centro Hospitalar Universitário de Santo António, Porto, Portugal

 UCIBIO - Applied Molecular Biosciences Unit, Biochemistry Laboratory, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal

Schwarz KB:
 Division of Pediatric Gastroenterology, Rady Children's Hospital San Diego, University of California San Diego, San Diego, California, USA

Brecelj J:
 Pediatric Gastroenterology, Hepatology and Nutrition, University Medical Center Ljubljana, Ljubljana, Slovenia

 Department of Pediatrics, Faculty of Medicine, University Medical Center Ljubljana, Ljubljana, Slovenia

Sanchez MC:
 Pediatric Gastroenterology and Hepatology Division, Hospital Italiano Buenos Aires, Buenos Aires, Argentina

Cavalieri ML:
 Pediatric Gastroenterology and Hepatology Division, Hospital Italiano Buenos Aires, Buenos Aires, Argentina

Tzivinikos C:
 Department of Paediatric Gastroenterology, Al Jalila Children's Specialty Hospital, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE

Wiecek S:
 Department of Pediatrics, Medical University of Silesia in Katowice, Katowice, Poland

Eshun J:
 Department of Pediatric Gastroenterology, The University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, Tennessee, USA

Kerkar N:
 Massachusetts General Hospital for Children, Boston, Massachusetts, USA

 University of Rochester Medical Center, Rochester, New York, USA

Mujawar Q:
 Section of Pediatric Gastroenterology, Department of Pediatrics, University of Manitoba, Winnipeg, Canada

Önal Z:
 Pediatric Gastroenterology, Hepatology and Nutrition Department, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey

Gonçalves C:
 European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Lisbon, Portugal

 Pediatric Gastroenterology/Hepatology Center, Lisbon, Portugal

Garcia J:
 Division of Pediatric Gastroenterology, Hepatology and Nutrition/Miami Transplant Institute, University of Miami, Miami, Florida, USA

Alam S:
 Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

Jimenez-Rivera C:
 Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Canada

Bujanda L:
 Department of Hepatology and Gastroenterology, Biodonostia Health Research Institute - Donostia University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain

Thompson RJ:
 Institute of Liver Studies, King's College London, London, UK

Hansen BE:
 Toronto General Hospital University Health Network, Toronto, Canada

 Institute of Health Policy, Management and Evaluation, Toronto, Canada

Spinner NB:
 Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

Gilbert MA:
 Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

Kamath BM:
 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Canada

 Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA