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SHR Neuro Krebs Kardio Lipid

Qiu, YL; Gong, JY; Feng, JY; Wang, RX; Han, J; Liu, T; Lu, Y; Li, LT; Zhang, MH; Sheps, JA; Wang, NL; Yan, YY; Li, JQ; Chen, L; Borchers, CH; Sipos, B; Knisely, AS; Ling, V; Xing, QH; Wang, JS.
Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ-glutamyltransferase cholestasis.
Hepatology. 2017; 65(5):1655-1669 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Knisely Alexander

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Number of Figures: 5
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Hereditary cholestasis in childhood and infancy with normal serum gamma-glutamyltransferase (GGT) activity is linked to several genes. Many patients, however, remain genetically undiagnosed. Defects in myosin VB (MYO5B; encoded by MYO5B) cause microvillus inclusion disease (MVID; MIM251850) with recurrent watery diarrhea. Cholestasis, reported as an atypical presentation in MVID, has been considered a side effect of parenteral alimentation. Here, however, we report on 10 patients who experienced cholestasis associated with biallelic, or suspected biallelic, mutations in MYO5B and who had neither recurrent diarrhea nor received parenteral alimentation. Seven of them are from two study cohorts, together comprising 31 undiagnosed low-GGT cholestasis patients; 3 are sporadic. Cholestasis in 2 patients was progressive, in 3 recurrent, in 2 transient, and in 3 uncategorized because of insufficient follow-up. Liver biopsy specimens revealed giant-cell change of hepatocytes and intralobular cholestasis with abnormal distribution of bile salt export pump (BSEP) at canaliculi, as well as coarse granular dislocation of MYO5B. Mass spectrometry of plasma demonstrated increased total bile acids, primary bile acids, and conjugated bile acids, with decreased free bile acids, similar to changes in BSEP-deficient patients. Literature review revealed that patients with biallelic mutations predicted to eliminate MYO5B expression were more frequent in typical MVID than in isolated-cholestasis patients (11 of 38 vs. 0 of 13). MYO5B deficiency may underlie 20% of previously undiagnosed low-GGT cholestasis. MYO5B deficiency appears to impair targeting of BSEP to the canalicular membrane with hampered bile acid excretion, resulting in a spectrum of cholestasis without diarrhea. (Hepatology 2017;65:1655-1669). © 2016 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
Find related publications in this database (using NLM MeSH Indexing)
ATP Binding Cassette Transporter, Subfamily B - blood
ATP Binding Cassette Transporter, Subfamily B - deficiency
ATP Binding Cassette Transporter, Subfamily B - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 11 -
ATP-Binding Cassette Transporters - metabolism
Bile Acids and Salts - blood
Cholestasis, Intrahepatic - blood
Cholestasis, Intrahepatic - genetics
Cholestasis, Intrahepatic - pathology
DNA Mutational Analysis -
Exome -
Female -
Humans -
Infant -
Infant, Newborn -
Liver - metabolism
Liver - pathology
Male -
Myosin Heavy Chains - genetics
Myosin Heavy Chains - metabolism
Myosin Type V - genetics
Myosin Type V - metabolism
Retrospective Studies -

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