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Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis

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 rec...

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Autores principales: Qiu, Yi‐Ling, Gong, Jing‐Yu, Feng, Jia‐Yan, Wang, Ren‐Xue, Han, Jun, Liu, Teng, Lu, Yi, Li, Li‐Ting, Zhang, Mei‐Hong, Sheps, Jonathan A., Wang, Neng‐Li, Yan, Yan‐Yan, Li, Jia‐Qi, Chen, Lian, Borchers, Christoph H., Sipos, Bence, Knisely, A.S., Ling, Victor, Xing, Qing‐He, Wang, Jian‐She
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413810/
https://www.ncbi.nlm.nih.gov/pubmed/28027573
http://dx.doi.org/10.1002/hep.29020
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author Qiu, Yi‐Ling
Gong, Jing‐Yu
Feng, Jia‐Yan
Wang, Ren‐Xue
Han, Jun
Liu, Teng
Lu, Yi
Li, Li‐Ting
Zhang, Mei‐Hong
Sheps, Jonathan A.
Wang, Neng‐Li
Yan, Yan‐Yan
Li, Jia‐Qi
Chen, Lian
Borchers, Christoph H.
Sipos, Bence
Knisely, A.S.
Ling, Victor
Xing, Qing‐He
Wang, Jian‐She
author_facet Qiu, Yi‐Ling
Gong, Jing‐Yu
Feng, Jia‐Yan
Wang, Ren‐Xue
Han, Jun
Liu, Teng
Lu, Yi
Li, Li‐Ting
Zhang, Mei‐Hong
Sheps, Jonathan A.
Wang, Neng‐Li
Yan, Yan‐Yan
Li, Jia‐Qi
Chen, Lian
Borchers, Christoph H.
Sipos, Bence
Knisely, A.S.
Ling, Victor
Xing, Qing‐He
Wang, Jian‐She
author_sort Qiu, Yi‐Ling
collection PubMed
description 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). Conclusion: 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).
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spelling pubmed-54138102017-05-15 Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis Qiu, Yi‐Ling Gong, Jing‐Yu Feng, Jia‐Yan Wang, Ren‐Xue Han, Jun Liu, Teng Lu, Yi Li, Li‐Ting Zhang, Mei‐Hong Sheps, Jonathan A. Wang, Neng‐Li Yan, Yan‐Yan Li, Jia‐Qi Chen, Lian Borchers, Christoph H. Sipos, Bence Knisely, A.S. Ling, Victor Xing, Qing‐He Wang, Jian‐She Hepatology Autoimmune, Cholestatic and Biliary Disease 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). Conclusion: 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). John Wiley and Sons Inc. 2017-03-23 2017-05 /pmc/articles/PMC5413810/ /pubmed/28027573 http://dx.doi.org/10.1002/hep.29020 Text en © 2016 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Autoimmune, Cholestatic and Biliary Disease
Qiu, Yi‐Ling
Gong, Jing‐Yu
Feng, Jia‐Yan
Wang, Ren‐Xue
Han, Jun
Liu, Teng
Lu, Yi
Li, Li‐Ting
Zhang, Mei‐Hong
Sheps, Jonathan A.
Wang, Neng‐Li
Yan, Yan‐Yan
Li, Jia‐Qi
Chen, Lian
Borchers, Christoph H.
Sipos, Bence
Knisely, A.S.
Ling, Victor
Xing, Qing‐He
Wang, Jian‐She
Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
title Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
title_full Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
title_fullStr Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
title_full_unstemmed Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
title_short Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
title_sort defects in myosin vb are associated with a spectrum of previously undiagnosed low γ‐glutamyltransferase cholestasis
topic Autoimmune, Cholestatic and Biliary Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413810/
https://www.ncbi.nlm.nih.gov/pubmed/28027573
http://dx.doi.org/10.1002/hep.29020
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