ArticleInternational journal of obesity (2005)2014
Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity.
Article in International journal of obesity (2005), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Multi-ancestry investigation of the genomics of erectile dysfunction.Nature communications · 2025Pooled it
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- NovelInternational journal of molecular sciences · 2026Article
- Effects of Rare Coding Variants in Severe Early-Onset Obesity Genes in the Population-Based UK Biobank Study.The Journal of clinical endocrinology and metabolism · 2025Article
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- Epigenome-wide association study in Chinese monozygotic twins identifies DNA methylation loci associated with blood pressure.Clinical epigenetics · 2023Article
- Genetics, epigenetics and transgenerational transmission of obesity in children.Frontiers in endocrinology · 2022Review
- A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis.International journal of molecular sciences · 2021Article
- Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases.Frontiers in neuroscience · 2020Review
- Novel Mutations in Obesity-related Genes in Turkish Children with Non-syndromic Early Onset Severe Obesity: A Multicentre StudyJournal of clinical research in pediatric endocrinology · 2019Article
- Cryptic breakpoint identified by whole-genome mate-pair sequencing in a rare paternally inherited complex chromosomal rearrangement.Molecular cytogenetics · 2018Article
- Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents.PloS one · 2017Article
- Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1.European journal of human genetics : EJHG · 2015Article
- Functional characterization of SIM1-associated enhancers.Human molecular genetics · 2014Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity.
methodsWe screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed.
resultsMutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type.
conclusionsIn this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.
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