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 AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
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
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
-
Anesthetic Pharmacology and Perioperative Considerations for Heart Transplantation
Current Clinical Pharmacology A Review on Natural Sources Derived Protein Nanoparticles as Anticancer Agents
Current Topics in Medicinal Chemistry S100A1: Structure, Function, and Therapeutic Potential
Current Chemical Biology The Fluctuations of Melatonin and Copeptin Levels in Blood Serum During Surgical Stress Regarding the Pediatric Population
Current Pediatric Reviews Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction
Current Drug Targets Beyond the Cardiac Myofilament: Hypertrophic Cardiomyopathy- Associated Mutations in Genes that Encode Calcium-Handling Proteins
Current Molecular Medicine subject Index To Volume 1
Current Molecular Medicine FoxO3a Governs Early Microglial Proliferation and Employs Mitochondrial Depolarization with Caspase 3, 8, and 9 Cleavage During Oxidant Induced Apoptosis
Current Neurovascular Research Leber's Hereditary Optic Neuropathy: Novel Views and Persisting Challenges
CNS & Neurological Disorders - Drug Targets Platelet and Soluble Glycoprotein VI - Novel Applications in Diagnosis and Therapy
Current Drug Targets Role of Sulfur Containing Amino Acids as an Adjuvant Therapy in the Prevention of Diabetes and its Associated Complications
Current Diabetes Reviews Cardiolipin Metabolism and the Role it Plays in Heart Failure and Mitochondrial Supercomplex Formation
Cardiovascular & Hematological Disorders-Drug Targets Evolution and Analysis of Heterogeneity in the Clinical Expression of Aortic Diseases Similar to Marfan’s Syndrome: Challenge and Art in Clinical Diagnosis
Current Rheumatology Reviews Use of Bromine-76 and Iodine-123 Radiohalogenated Tracers in the Drug Development Process
Current Pharmaceutical Design Peroxisome Proliferator-Activated Receptor (PPAR) in Metabolic Syndrome and Type 2 Diabetes Mellitus
Current Diabetes Reviews Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry Genetic Polymorphism of Organic Anion and Cation Transporters: Pharmacokinetic and Pharmacodynamic Consequences in Pharmacotherapy
Current Pharmacogenomics Cardiovascular disease management through restrained inflammatory responses
Current Pharmaceutical Design Cardiac Dysfunction in Rats with Dietary-Induced Insulin Resistance Associated with Pharmacologically-induced Dyslipidemia
Current Pharmaceutical Design Natural Polyphenols and Cardioprotection
Mini-Reviews in Medicinal Chemistry