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SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN)
PURPOSE: Biallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholest...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989927/ https://www.ncbi.nlm.nih.gov/pubmed/29419818 http://dx.doi.org/10.1038/gim.2017.260 |
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author | Lenz, Dominic McClean, Patricia Kansu, Aydan Bonnen, Penelope E Ranucci, Giusy Thiel, Christian Straub, Beate K Harting, Inga Alhaddad, Bader Dimitrov, Bianca Kotzaeridou, Urania Wenning, Daniel Iorio, Raffaele Himes, Ryan W Kuloğlu, Zarife Blakely, Emma L Taylor, Robert W Meitinger, Thomas Kölker, Stefan Prokisch, Holger Hoffmann, Georg F Haack, Tobias B Staufner, Christian |
author_facet | Lenz, Dominic McClean, Patricia Kansu, Aydan Bonnen, Penelope E Ranucci, Giusy Thiel, Christian Straub, Beate K Harting, Inga Alhaddad, Bader Dimitrov, Bianca Kotzaeridou, Urania Wenning, Daniel Iorio, Raffaele Himes, Ryan W Kuloğlu, Zarife Blakely, Emma L Taylor, Robert W Meitinger, Thomas Kölker, Stefan Prokisch, Holger Hoffmann, Georg F Haack, Tobias B Staufner, Christian |
author_sort | Lenz, Dominic |
collection | PubMed |
description | PURPOSE: Biallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholestasis or acute liver failure has not been studied; furthermore, little is known regarding the hepatic phenotype. METHODS: We aimed to identify patients with SCYL1 variants within an exome-sequencing study of individuals with infantile cholestasis or acute liver failure of unknown etiology. Deep clinical and biochemical phenotyping plus analysis of liver biopsies and functional studies on fibroblasts were performed. RESULTS: Seven patients from five families with biallelic SCYL1 variants were identified. The main clinical phenotype was recurrent low γ-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset (CALFAN syndrome). Liver crises were triggered by febrile infections and were transient, but fibrosis developed. Functional studies emphasize that SCYL1 deficiency is linked to impaired intracellular trafficking. CONCLUSION: SCYL1 deficiency can cause recurrent low-GGT cholestatic liver dysfunction in conjunction with a variable neurological phenotype. Like NBAS deficiency, it is a member of the emerging group of congenital disorders of intracellular trafficking causing hepatopathy. |
format | Online Article Text |
id | pubmed-5989927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-59899272018-11-27 SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN) Lenz, Dominic McClean, Patricia Kansu, Aydan Bonnen, Penelope E Ranucci, Giusy Thiel, Christian Straub, Beate K Harting, Inga Alhaddad, Bader Dimitrov, Bianca Kotzaeridou, Urania Wenning, Daniel Iorio, Raffaele Himes, Ryan W Kuloğlu, Zarife Blakely, Emma L Taylor, Robert W Meitinger, Thomas Kölker, Stefan Prokisch, Holger Hoffmann, Georg F Haack, Tobias B Staufner, Christian Genet Med Article PURPOSE: Biallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholestasis or acute liver failure has not been studied; furthermore, little is known regarding the hepatic phenotype. METHODS: We aimed to identify patients with SCYL1 variants within an exome-sequencing study of individuals with infantile cholestasis or acute liver failure of unknown etiology. Deep clinical and biochemical phenotyping plus analysis of liver biopsies and functional studies on fibroblasts were performed. RESULTS: Seven patients from five families with biallelic SCYL1 variants were identified. The main clinical phenotype was recurrent low γ-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset (CALFAN syndrome). Liver crises were triggered by febrile infections and were transient, but fibrosis developed. Functional studies emphasize that SCYL1 deficiency is linked to impaired intracellular trafficking. CONCLUSION: SCYL1 deficiency can cause recurrent low-GGT cholestatic liver dysfunction in conjunction with a variable neurological phenotype. Like NBAS deficiency, it is a member of the emerging group of congenital disorders of intracellular trafficking causing hepatopathy. Nature Publishing Group US 2018-02-08 2018 /pmc/articles/PMC5989927/ /pubmed/29419818 http://dx.doi.org/10.1038/gim.2017.260 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lenz, Dominic McClean, Patricia Kansu, Aydan Bonnen, Penelope E Ranucci, Giusy Thiel, Christian Straub, Beate K Harting, Inga Alhaddad, Bader Dimitrov, Bianca Kotzaeridou, Urania Wenning, Daniel Iorio, Raffaele Himes, Ryan W Kuloğlu, Zarife Blakely, Emma L Taylor, Robert W Meitinger, Thomas Kölker, Stefan Prokisch, Holger Hoffmann, Georg F Haack, Tobias B Staufner, Christian SCYL1 variants cause a syndrome with low γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN) |
title | SCYL1 variants cause a syndrome with low
γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration
(CALFAN) |
title_full | SCYL1 variants cause a syndrome with low
γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration
(CALFAN) |
title_fullStr | SCYL1 variants cause a syndrome with low
γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration
(CALFAN) |
title_full_unstemmed | SCYL1 variants cause a syndrome with low
γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration
(CALFAN) |
title_short | SCYL1 variants cause a syndrome with low
γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration
(CALFAN) |
title_sort | scyl1 variants cause a syndrome with low
γ-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration
(calfan) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989927/ https://www.ncbi.nlm.nih.gov/pubmed/29419818 http://dx.doi.org/10.1038/gim.2017.260 |
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