Genetic studies of intellectual disability and identification of monogenic causes of obesity in humans have made immense contribution toward the understanding of the brain and control of body mass. The leptin > melanocortin > SIM1 pathway is dysregulated in multiple monogenic human obesity syndromes but its downstream targets are still unknown. In ten individuals from six families, with overlapping 6q16.1 deletions, we describe a disorder of variable developmental delay, intellectual disability, and susceptibility to obesity and hyperphagia. The 6q16.1 deletions segregated with the phenotype in multiplex families and were shown to be de novo in four families, and there was dramatic phenotypic overlap among affected individuals who were independently ascertained without bias from clinical features. Analysis of the deletions revealed a ∼350 kb critical region on chromosome 6q16.1 that encompasses a gene for proneuronal transcription factor POU3F2, which is important for hypothalamic development and function. Using morpholino and mutant zebrafish models, we show that POU3F2 lies downstream of SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. Our work helps to further delineate the neuro-endocrine control of energy balance/body mass and demonstrates that this molecular pathway is conserved across multiple species.

INTRODUCTION: In 2015 the FDA conducted a review on Essure after a significant number of patient complaints were reported. Multiple sources were used to gather information on adverse reports including social media through “social listening” [1]. We aim to quantify the number of web searches related to Essure and to correlate these findings with FDA complaints. METHODS: We used Bing Adwords, a web search tool to quantify the monthly number of searches for 2015 until July 2016. Search terms included: Essure, Essure procedure, tubal occlusion, tubal ligation. We also quantified the number of FDA complaints during the same time. RESULTS: The average number of monthly searches on Essure or Essure procedure was 5,849 in 2015 and 4,824 in 2016 (18% decrease). In September 2015 and March of 2016 the number of searches increased to 7,760 and 7,260 searches, respectively. Similarly, the number of FDA reports decreased from an average of 500 per month in 2015 to 380 per month in 2016 (24% decrease) [2]. Tubal occlusion and tubal ligation searches remained in the same range for 2015-2016. CONCLUSION: There was a similar decreasing trend for both the number of Essure searches and the number of FDA reports in 2016, suggesting that public interest in Essure began to decline after 2015. Web searches spiked during the FDA review and update in September 2015 and March 2016. This trend was not observed for tubal occlusion searches, perhaps because the general population does not use this term. This method could be useful for population health interest research.