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Journal of Medical Genetics Dec 2023Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the gene, which encodes a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the gene, which encodes a centrosome-associated protein involved in the regulation of several ciliary and extraciliary processes, such as centrosome cohesion, apoptosis, cell cycle control and receptor trafficking. The type of variant associated with ALMS is mostly complete loss-of-function variants (97%) and they are mainly located in exons 8, 10 and 16 of the gene. Other studies in the literature have tried to establish a genotype-phenotype correlation in this syndrome with limited success. The difficulty in recruiting a large cohort in rare diseases is the main barrier to conducting this type of study.
METHODS
In this study we collected all cases of ALMS published to date. We created a database of patients who had a genetic diagnosis and an individualised clinical history. Lastly, we attempted to establish a genotype-phenotype correlation using the truncation site of the patient's longest allele as a grouping criteria.
RESULTS
We collected a total of 357 patients, of whom 227 had complete clinical information, complete genetic diagnosis and meta-information on sex and age. We have seen that there are five variants with high frequency, with p.(Arg2722Ter) being the most common variant, with 28 alleles. No gender differences in disease progression were detected. Finally, truncating variants in exon 10 seem to be correlated with a higher prevalence of liver disorders in patients with ALMS.
CONCLUSION
Pathogenic variants in exon 10 of the gene were associated with a higher prevalence of liver disease. However, the location of the variant in the gene does not have a major impact on the phenotype developed by the patient.
Topics: Humans; Alstrom Syndrome; Cell Cycle Proteins; Phenotype; Exons; Genetic Association Studies
PubMed: 37321834
DOI: 10.1136/jmg-2023-109175 -
Journal of Pediatric Endocrinology &... Jun 2022Investigation of monogenic obesity (MO), a rare condition caused by a single gene variant(s), especially in consanguineous populations, is a powerful approach... (Review)
Review
BACKGROUND
Investigation of monogenic obesity (MO), a rare condition caused by a single gene variant(s), especially in consanguineous populations, is a powerful approach for obtaining novel insights into the genetic alterations involved. Here, we present a systematic review of the genetics of MO in the 22 Arab countries and apply protein modeling to the missense variants reported.
METHODS
We searched four literature databases (PubMed, Web of Science, Science Direct and Scopus) from the time of their first creation until December 2020, utilizing broad search terms to capture all genetic studies related to MO in the Arab countries. Only articles published in peer-reviewed journals involving subjects from at least one of the 22 Arab countries and dealing with genetic variants related to MO were included. Protein modelling of the variants identified was performed using PyMOL.
RESULTS
The 30 cases with severe early-onset obesity identified in 13 studies carried 14 variants in five genes (). All of these variants were pathogenic, homozygous and carried by members of consanguineous families.
CONCLUSION
Despite the elevated presence of consanguinity in the Arab countries, the genetic origins of MO remain largely unexplained and require additional studies, both of a genetic and functional character.
Topics: Arab World; Consanguinity; Homozygote; Humans; Mutation; Obesity
PubMed: 35437977
DOI: 10.1515/jpem-2021-0710 -
Journal of Advanced Veterinary and... Mar 2020Several animals have been in the limelight of basic research associated with metabolic diseases like obesity. Obesity can be considered as a significant public health... (Review)
Review
Several animals have been in the limelight of basic research associated with metabolic diseases like obesity. Obesity can be considered as a significant public health concern in the world. It raises the chances for a variety of disease conditions that includes diabetes, hypertension, liver disease, and cancers, which, in turn, decreases the overall lifespan of adult men and women. The World Health Organization has considered obesity as a global epidemic. Researchers have made several attempts to classify human obesity, but none have been successful. Animal obesity can be classified based on their etiology; however, till now, no animal model of obesity can replicate models of the human condition, they have only provided clues into the causes, aftermaths, and preventive remedy to human adiposity. Over the years, there are varieties of animal models used to induce obesity. Some of them include monogenic, polygenic, surgical, seasonal, and other models of obesity. Apart from the advantages of these models, most of them are accompanied by limitations. The primary purpose of this review is, therefore, to highlight the several models with their advantages and limitations. By knowing the benefits and limitations of animal models of obesity, researchers may be at liberty to select the appropriate one for the study of obesity.
PubMed: 32219116
DOI: 10.5455/javar.2020.g399