Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations
| Autor: | S Ünal, J Koeglmeier, M Meissl, H Ayyıldız Civan, J Melek, T Siahanidou, A M Demir, Patrick Gerner, J H Montoya, Duba H-C., Denise Aldrian, A Koutroumpa, Sahar Mansour, Michael W. Hess, Murat Cakir, Georg F. Vogel, Thomas Müller, J Hornova, T K Frey, Aysel Ünlüsoy Aksu, Y Rachman, Ekkehard Sturm, Andreas R. Janecke, G Düker, M Miqdady, Lukas A. Huber, R Lima, Frank M. Ruemmele, Carsten Posovszky, J Hertecant, Holm H. Uhlig, E Ramos Boluda, Stefan Wirth, Raffi Lev-Tzion, C Deppisch, R Lanzersdorfer, Merit M. Tabbers, Simone Kathemann, Yaron Avitzur |
|---|---|
| Přispěvatelé: | Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Diarrhea
0301 basic medicine medicine.medical_specialty Genetic counseling Myosin Medizin lcsh:Medicine Disease Myosins Gastroenterology Article 03 medical and health sciences 0302 clinical medicine Internal medicine Genotype lack of protein Medicine Enteropathy ddc:610 tail domain Lack of protein Cholestasis business.industry Genotype–phenotype correlation lcsh:R Progressive familial intrahepatic cholestasis General Medicine genotype–phenotype correlation Tail domain medicine.disease congenital diarrheal diseases Phenotype PFIC Cholestase Transplantation Durchfall 030104 developmental biology Parenteral nutrition Kontraktile Proteine MYO5B enteropathy YO5B 030211 gastroenterology & hepatology progressive familial intrahepatic cholestasis business myosin Vbin DDC 610 / Medicine & health myosin Vb microvillus inclusion disease |
| Zdroj: | Journal of Clinical Medicine, Vol 10, Iss 481, p 481 (2021) Journal of clinical medicine, 10(3):481, 1-15. Multidisciplinary Digital Publishing Institute (MDPI) Journal of Clinical Medicine Volume 10 Issue 3 |
| ISSN: | 2077-0383 |
| Popis: | 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. publishedVersion |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|