Journal of Clinical Medicine (Jan 2021)
Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations
- Denise Aldrian,
- Georg F. Vogel,
- Teresa K. Frey,
- Hasret Ayyıldız Civan,
- Aysel Ünlüsoy Aksu,
- Yaron Avitzur,
- Esther Ramos Boluda,
- Murat Çakır,
- Arzu Meltem Demir,
- Caroline Deppisch,
- Hans-Christoph Duba,
- Gesche Düker,
- Patrick Gerner,
- Jozef Hertecant,
- Jarmila Hornová,
- Simone Kathemann,
- Jutta Koeglmeier,
- Arsinoi Koutroumpa,
- Roland Lanzersdorfer,
- Raffi Lev-Tzion,
- Rosa Lima,
- Sahar Mansour,
- Manfred Meissl,
- Jan Melek,
- Mohamad Miqdady,
- Jorge Hernan Montoya,
- Carsten Posovszky,
- Yelena Rachman,
- Tania Siahanidou,
- Merit Tabbers,
- Holm H. Uhlig,
- Sevim Ünal,
- Stefan Wirth,
- Frank M. Ruemmele,
- Michael W. Hess,
- Lukas A. Huber,
- Thomas Müller,
- Ekkehard Sturm,
- Andreas R. Janecke
Affiliations
- Denise Aldrian
- Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Georg F. Vogel
- Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Teresa K. Frey
- Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Hasret Ayyıldız Civan
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Health Science University, Sadi Konuk Education and Research Hospital, 34147 Istanbul, Turkey
- Aysel Ünlüsoy Aksu
- University of Health Sciences, Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, 06120 Ankara, Turkey
- Yaron Avitzur
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
- Esther Ramos Boluda
- Intestinal Rehabilitation Unit, Pediatric Gastroenterology and Nutrition Unit, University Hospital La Paz, 28046 Madrid, Spain
- Murat Çakır
- Departments of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey
- Arzu Meltem Demir
- Ankara Child Health and Diseases, Training and Research Hospital, Pediatric Gastroenterology, 06130 Ankara, Turkey
- Caroline Deppisch
- Universitätsklinik für Kinder- und Jugendmedizin Tübingen, Pädiatrische Gastroenterologie und Hepatologie, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany
- Hans-Christoph Duba
- Department of Medical Genetics, Kepler University Hospital, School of Medicine, Johannes Kepler University, A-4020 Linz, Austria
- Gesche Düker
- Department for Pediatric Gastroenterology and Hepatology, University Children’s Hospital Bonn, 53127 Bonn, Germany
- Patrick Gerner
- Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
- Jozef Hertecant
- Genetics/Metabolics Service, Tawam Hospital, Al Ain 15258, United Arab Emirates
- Jarmila Hornová
- Department of Pediatrics, Faculty of Medicine, Comenius University, National Institute of Children Diseases, 814 99 Bratislava, Slovakia
- Simone Kathemann
- Department for Pediatric Nephrology, Gastroenterology, Endocrinology and Transplant Medicine, Clinic for Pediatrics II, University Children’s Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Jutta Koeglmeier
- Department of Paediatric Gastroenterology, Unit of Nutrition and Intestinal Failure Rehabilitation, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK
- Arsinoi Koutroumpa
- Aghia Sofia Children’s Hospital, Neonatal Intensive Care Unit B, 115 27 Athens, Greece
- Roland Lanzersdorfer
- Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, A-4020 Linz, Austria
- Raffi Lev-Tzion
- Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
- Rosa Lima
- Unidade de Gastrenterologia Pediátrica-Centro Hospitalar do Porto, 4099-001 Porto, Portugal
- Sahar Mansour
- SW Thames Regional Genetics Service, St. George’s University NHS Foundation Trust, London SW17 0QT, UK
- Manfred Meissl
- Department of Neonatology, Johannes Kepler University Linz, A-4020 Linz, Austria
- Jan Melek
- Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine in Hradec Králové, Charles University, 110 00 Prague, Czech Republic
- Mohamad Miqdady
- Department of Pediatric, Sheikh Khalifa Medical City, College of Medicine & Health Sciences, Khalife University, Abu Dhabi 127788, United Arab Emirates
- Jorge Hernan Montoya
- Hospital Universitario San Vicente de Paúl, Medellín, Antioquia 50022, Colombia
- Carsten Posovszky
- Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstr. 24, 89075 Ulm, Germany
- Yelena Rachman
- Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
- Tania Siahanidou
- First Department of Pediatrics, Athens University Medical School, 11527 Athens, Greece
- Merit Tabbers
- Emma Children’s Hospital/AMC, 1105 Amsterdam, The Netherlands
- Holm H. Uhlig
- Translational Gastroenterology Unit, University of Oxford, Oxford OX3 9DU, UK
- Sevim Ünal
- Ankara Child Health and Diseases, Training and Research Hospital, Neonatology, 06120 Ankara, Turkey
- Stefan Wirth
- Department of Paediatrics, Helios Medical Centre Wuppertal, Witten-Herdecke University, 58455 Witten, Germany
- Frank M. Ruemmele
- Assistance Publique–Hôpitaux de Paris, Hôpital Universitaire Necker Enfants, Malades Service de Gastroentérologie, Hépatologie et Nutrition Pédiatrique, 149, Rue de Sèvres, 75015 Paris, France
- Michael W. Hess
- Institute of Histology and Embryology, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Lukas A. Huber
- Division of Cell Biology, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Thomas Müller
- Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- Ekkehard Sturm
- Children’s Hospital Tübingen, 72076 Tübingen, Germany
- Andreas R. Janecke
- Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria
- DOI
- https://doi.org/10.3390/jcm10030481
- Journal volume & issue
-
Vol. 10,
no. 3
p. 481
Abstract
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.
Keywords
- congenital diarrheal diseases
- enteropathy
- microvillus inclusion disease
- MYO5B
- myosin Vb
- progressive familial intrahepatic cholestasis