Abstract
Alstrom 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.
Alstrom 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 Alstrom 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.
Keywords: ALMS1, Alstrom syndrome, ciliopathy, truncal obesity, insulin resistance, hyperinsulinemia, cone-rod dystrophy, type 2 diabetes, hypertriglyceridemia, cardiomyopathy
Current Genomics
Title: Alstrom Syndrome: Genetics and Clinical Overview
Volume: 12 Issue: 3
Author(s): Jan D. Marshall, Pietro Maffei, Gayle B. Collin and Jurgen K. Naggert
Affiliation:
Keywords: ALMS1, Alstrom syndrome, ciliopathy, truncal obesity, insulin resistance, hyperinsulinemia, cone-rod dystrophy, type 2 diabetes, hypertriglyceridemia, cardiomyopathy
Abstract: Alstrom 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.
Alstrom 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 Alstrom 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.
Export Options
About this article
Cite this article as:
D. Marshall Jan, Maffei Pietro, B. Collin Gayle and K. Naggert Jurgen, Alstrom Syndrome: Genetics and Clinical Overview, Current Genomics 2011; 12 (3) . https://dx.doi.org/10.2174/138920211795677912
DOI https://dx.doi.org/10.2174/138920211795677912 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Historical Aspects and Relevance of the Human Coronary Collateral Circulation
Current Cardiology Reviews Inhibition of Matrix Metalloproteinases (MMPs) as a Potential Strategy to Ameliorate Hypertension-Induced Cardiovascular Alterations
Current Drug Targets The Application of NMR Spectroscopy for the Study of Heart Failure
Current Pharmaceutical Design Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity
Current Medicinal Chemistry Membrane Rafts in the Respiratory System
Current Respiratory Medicine Reviews Role of Antioxidants in Redox Regulation of Diabetic Cardiovascular Complications
Current Pharmaceutical Biotechnology The Role of Klotho Protein in Chronic Kidney Disease: Studies in Animals and Humans
Current Protein & Peptide Science Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy
Current Cardiology Reviews Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists
Current Alzheimer Research Cardiac Tissue Engineering
Recent Patents on Regenerative Medicine Bisphenol A as a Factor in the Mosaic of Autoimmunity
Endocrine, Metabolic & Immune Disorders - Drug Targets Muscle Development and Regeneration in Normal and Pathological Conditions: Learning from Drosophila
Current Pharmaceutical Design Smoking and Hypertension: Effects on Clinical, Biochemical and Pathological Variables Due to Isolated or Combined Action on Cardiovascular System
Current Pharmaceutical Design Perinatal Exposure to Bisphenol A and Developmental Programming of the Cardiovascular Changes in the Offspring
Current Medicinal Chemistry Oxidative stress and myocarditis
Current Pharmaceutical Design The Heart and Brain Imaging in Lone Atrial Fibrillation – Are We Surprised?
Current Pharmaceutical Design MCP-1/CCL2 as a Therapeutic Target in Myocardial Infarction and Ischemic Cardiomyopathy
Inflammation & Allergy - Drug Targets (Discontinued) Endocannabinoids in Liver Disease and Hepatic Encephalopathy
Current Pharmaceutical Design Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease
Current Cardiology Reviews Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease
Current Topics in Medicinal Chemistry