TY - JOUR
T1 - Congenital diarrhea and cholestatic liver disease: Phenotypic spectrum associated with myo5b mutations
AU - Aldrian, Denise
AU - Vogel, Georg F.
AU - Frey, Teresa K.
AU - Civan, Hasret Ayyıldız
AU - Aksu, Aysel Ünlüsoy
AU - Avitzur, Yaron
AU - Ramos, Ester Boluda
AU - Çakır, Murat
AU - Demir, Arzu Meltem
AU - Deppisch, Caroline
AU - Duba, Hans-Christoph
AU - Düker, Gesche
AU - Gerner, Patrick
AU - Hertecant, Jozef
AU - Hornová, Jarmila
AU - Kathemann, Simone
AU - Koeglmeier, Jutta
AU - Koutroumpa, Arsinoi
AU - Lanzersdorfer, Roland
AU - Lev-Tzion, Raffi
AU - Lima, Rosa
AU - Mansour, Sahar
AU - Meissl, Manfred
AU - Melek, Jan
AU - Miqdady, Mohamad
AU - Montoya, Jorge Hernan
AU - Posovszky, Carsten
AU - Rachman, Yelena
AU - Siahanidou, Tania
AU - Tabbers, Merit
AU - Uhlig, Holm H.
AU - Ünal, Sevim
AU - Wirth, Stefan
AU - Ruemmele, Frank M.
AU - Hess, Michael W.
AU - Huber, Lukas A.
AU - Müller, Thomas
AU - Sturm, Ekkehard
AU - Janecke, Andreas R.
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 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 in-tractable 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.
AB - 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 in-tractable 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.
KW - Congenital diarrheal diseases
KW - Enteropathy
KW - Genotype–phenotype correlation
KW - Lack of protein
KW - MYO5B
KW - Microvillus inclusion disease
KW - Myosin Vb
KW - PFIC
KW - Progressive familial intrahepatic cholestasis
KW - Tail domain
UR - http://www.scopus.com/inward/record.url?scp=85114041266&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/jcm10030481
DO - https://doi.org/10.3390/jcm10030481
M3 - Article
C2 - 33525641
SN - 2077-0383
VL - 10
SP - 1
EP - 15
JO - Journal of clinical medicine
JF - Journal of clinical medicine
IS - 3
M1 - 481
ER -