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ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits
Alström syndrome (AS) is characterised by metabolic deficits, retinal dystrophy, sensorineural hearing loss, dilated cardiomyopathy and multi-organ fibrosis. Elucidating the function of the mutated gene, ALMS1, is critical for the development of specific treatments and may uncover pathways relevant...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327082/ https://www.ncbi.nlm.nih.gov/pubmed/30421101 http://dx.doi.org/10.1007/s00109-018-1714-x |
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author | Hearn, Tom |
author_facet | Hearn, Tom |
author_sort | Hearn, Tom |
collection | PubMed |
description | Alström syndrome (AS) is characterised by metabolic deficits, retinal dystrophy, sensorineural hearing loss, dilated cardiomyopathy and multi-organ fibrosis. Elucidating the function of the mutated gene, ALMS1, is critical for the development of specific treatments and may uncover pathways relevant to a range of other disorders including common forms of obesity and type 2 diabetes. Interest in ALMS1 is heightened by the recent discovery of its involvement in neonatal cardiomyocyte cell cycle arrest, a process with potential relevance to regenerative medicine. ALMS1 encodes a ~ 0.5 megadalton protein that localises to the base of centrioles. Some studies have suggested a role for this protein in maintaining centriole-nucleated sensory organelles termed primary cilia, and AS is now considered to belong to the growing class of human genetic disorders linked to ciliary dysfunction (ciliopathies). However, mechanistic details are lacking, and recent studies have implicated ALMS1 in several processes including endosomal trafficking, actin organisation, maintenance of centrosome cohesion and transcription. In line with a more complex picture, multiple isoforms of the protein likely exist and non-centrosomal sites of localisation have been reported. This review outlines the evidence for both ciliary and extra-ciliary functions of ALMS1. |
format | Online Article Text |
id | pubmed-6327082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-63270822019-01-25 ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits Hearn, Tom J Mol Med (Berl) Review Alström syndrome (AS) is characterised by metabolic deficits, retinal dystrophy, sensorineural hearing loss, dilated cardiomyopathy and multi-organ fibrosis. Elucidating the function of the mutated gene, ALMS1, is critical for the development of specific treatments and may uncover pathways relevant to a range of other disorders including common forms of obesity and type 2 diabetes. Interest in ALMS1 is heightened by the recent discovery of its involvement in neonatal cardiomyocyte cell cycle arrest, a process with potential relevance to regenerative medicine. ALMS1 encodes a ~ 0.5 megadalton protein that localises to the base of centrioles. Some studies have suggested a role for this protein in maintaining centriole-nucleated sensory organelles termed primary cilia, and AS is now considered to belong to the growing class of human genetic disorders linked to ciliary dysfunction (ciliopathies). However, mechanistic details are lacking, and recent studies have implicated ALMS1 in several processes including endosomal trafficking, actin organisation, maintenance of centrosome cohesion and transcription. In line with a more complex picture, multiple isoforms of the protein likely exist and non-centrosomal sites of localisation have been reported. This review outlines the evidence for both ciliary and extra-ciliary functions of ALMS1. Springer Berlin Heidelberg 2018-11-12 2019 /pmc/articles/PMC6327082/ /pubmed/30421101 http://dx.doi.org/10.1007/s00109-018-1714-x Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Review Hearn, Tom ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
title | ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
title_full | ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
title_fullStr | ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
title_full_unstemmed | ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
title_short | ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
title_sort | alms1 and alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327082/ https://www.ncbi.nlm.nih.gov/pubmed/30421101 http://dx.doi.org/10.1007/s00109-018-1714-x |
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