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Citations to this article

Rare variants in single-minded 1 (SIM1) are associated with severe obesity
Shwetha Ramachandrappa, … , Murray L. Whitelaw, I. Sadaf Farooqi
Shwetha Ramachandrappa, … , Murray L. Whitelaw, I. Sadaf Farooqi
Published June 17, 2013
Citation Information: J Clin Invest. 2013;123(7):3042-3050. https://doi.org/10.1172/JCI68016.
View: Text | PDF | Erratum
Research Article Article has an altmetric score of 43

Rare variants in single-minded 1 (SIM1) are associated with severe obesity

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Abstract

Single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor involved in the development and function of the paraventricular nucleus of the hypothalamus. Obesity has been reported in Sim1 haploinsufficient mice and in a patient with a balanced translocation disrupting SIM1. We sequenced the coding region of SIM1 in 2,100 patients with severe, early onset obesity and in 1,680 controls. Thirteen different heterozygous variants in SIM1 were identified in 28 unrelated severely obese patients. Nine of the 13 variants significantly reduced the ability of SIM1 to activate a SIM1-responsive reporter gene when studied in stably transfected cells coexpressing the heterodimeric partners of SIM1 (ARNT or ARNT2). SIM1 variants with reduced activity cosegregated with obesity in extended family studies with variable penetrance. We studied the phenotype of patients carrying variants that exhibited reduced activity in vitro. Variant carriers exhibited increased ad libitum food intake at a test meal, normal basal metabolic rate, and evidence of autonomic dysfunction. Eleven of the 13 probands had evidence of a neurobehavioral phenotype. The phenotypic similarities between patients with SIM1 deficiency and melanocortin 4 receptor (MC4R) deficiency suggest that some of the effects of SIM1 deficiency on energy homeostasis are mediated by altered melanocortin signaling.

Authors

Shwetha Ramachandrappa, Anne Raimondo, Anna M.G. Cali, Julia M. Keogh, Elana Henning, Sadia Saeed, Amanda Thompson, Sumedha Garg, Elena G. Bochukova, Soren Brage, Victoria Trowse, Eleanor Wheeler, Adrienne E. Sullivan, Mehul Dattani, Peter E. Clayton, Vippan Datta, John B. Bruning, Nick J. Wareham, Stephen O’Rahilly, Daniel J. Peet, Ines Barroso, Murray L. Whitelaw, I. Sadaf Farooqi

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 2 8 3 6 10 7 7 4 9 6 7 8 3 1 81
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2014 (8)

Title and authors Publication Year
A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited human obesity
J Philippe, P Stijnen, D Meyre, FD Graeve, D Thuillier, J Delplanque, G Gyapay, O Sand, JW Creemers, P Froguel, A Bonnefond
International Journal of Obesity 2014
Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1
LE Khattabi, F Guimiot, E Pipiras, J Andrieux, C Baumann, S Bouquillon, AL Delezoide, B Delobel, F Demurger, H Dessuant, S Drunat, C Dubourg, C Dupont, L Faivre, M Holder-Espinasse, S Jaillard, H Journel, S Lyonnet, V Malan, A Masurel, N Marle, C Missirian, A Moerman, A Moncla, S Odent, O Palumbo, P Palumbo, A Ravel, S Romana, AC Tabet, M Valduga, M Vermelle, M Carella, JM Dupont, A Verloes, B Benzacken, A Delahaye
European Journal of Human Genetics 2014
Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity
S Bouret, BE Levin, SE Ozanne
Physiological reviews 2014
Genetic strategies to understand physiological pathways regulating body weight
S Farooqi
Mammalian Genome 2014
Neurobiology of food intake in health and disease
GJ Morton, TH Meek, MW Schwartz
Nature Reviews Neuroscience 2014
Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function
DC Bersten, JB Bruning, DJ Peet, ML Whitelaw
PloS one 2014
Inducible Neuronal Inactivation of Sim1 in Adult Mice Causes Hyperphagic Obesity
KP Tolson, T Gemelli, D Meyer, U Yazdani, J Kozlitina, AR Zinn
Endocrinology 2014
Hindbrain Oxytocin Receptors Contribute to the Effects of Circulating Oxytocin on Food Intake in Male Rats
JM Ho, VT Anekonda, BW Thompson, M Zhu, RW Curry, BH Hwang, GJ Morton, MW Schwartz, DG Baskin, SM Appleyard, JE Blevins
Endocrinology 2014

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