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Alström Syndrome: Genetics and Clinical Overview

Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic...

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Autores principales: Marshall, Jan D, Maffei, Pietro, Collin, Gayle B, Naggert, Jürgen K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers Ltd 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137007/
https://www.ncbi.nlm.nih.gov/pubmed/22043170
http://dx.doi.org/10.2174/138920211795677912
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author Marshall, Jan D
Maffei, Pietro
Collin, Gayle B
Naggert, Jürgen K
author_facet Marshall, Jan D
Maffei, Pietro
Collin, Gayle B
Naggert, Jürgen K
author_sort Marshall, Jan D
collection PubMed
description Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background. Alström syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet-Biedl syndrome. Studies involving murine and cellular models of Alström syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alström syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population.
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spelling pubmed-31370072011-11-01 Alström Syndrome: Genetics and Clinical Overview Marshall, Jan D Maffei, Pietro Collin, Gayle B Naggert, Jürgen K Curr Genomics Article Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background. Alström syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet-Biedl syndrome. Studies involving murine and cellular models of Alström syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alström syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population. Bentham Science Publishers Ltd 2011-05 /pmc/articles/PMC3137007/ /pubmed/22043170 http://dx.doi.org/10.2174/138920211795677912 Text en ©2011 Bentham Science Publishers Ltd http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Marshall, Jan D
Maffei, Pietro
Collin, Gayle B
Naggert, Jürgen K
Alström Syndrome: Genetics and Clinical Overview
title Alström Syndrome: Genetics and Clinical Overview
title_full Alström Syndrome: Genetics and Clinical Overview
title_fullStr Alström Syndrome: Genetics and Clinical Overview
title_full_unstemmed Alström Syndrome: Genetics and Clinical Overview
title_short Alström Syndrome: Genetics and Clinical Overview
title_sort alström syndrome: genetics and clinical overview
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137007/
https://www.ncbi.nlm.nih.gov/pubmed/22043170
http://dx.doi.org/10.2174/138920211795677912
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