Congenital diarrhea and cholestatic liver disease: phenotypic spectrum associated with MYO5B mutations
Vogel, Georg F.
Frey, Teresa K.
Ayyıldız Civan, Hasret
Aksu, Aysel Ünlüsoy
Journal of Clinical Medicine ; 10 (2021), 3. - Art.-Nr. 481. - eISSN 2077-0383
Link to original publicationhttps://dx.doi.org/10.3390/jcm10030481
InstitutionsUKU. Klinik für Kinder- und Jugendmedizin
Document versionpublished version (publisher's PDF)
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.
Is supplemented byhttps://www.mdpi.com/2077-0383/10/3/481/s1
Subject headings[GND]: Cholestase | Durchfall | Myosin
[MeSH]: Diarrhea | Cholestasis | Myosins | Kontraktile Proteine
[Free subject headings]: congenital diarrheal diseases | enteropathy | microvillus inclusion disease | MYO5B | myosin Vb | progressive familial intrahepatic cholestasis | PFIC | genotype–phenotype correlation | lack of protein | tail domain
[DDC subject group]: DDC 610 / Medicine & health
LicenseCC BY 4.0 International
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DOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-43530