👤 Ukasha Moazzam

Early-onset severe obesity is rare and largely treatment-resistant to standard measures. Etiologies include syndromic disorders (Prader-Willi, Bardet-Biedl and Alström syndromes), monogenic defects of appetite-regulating pathways - most significantly melanocortin-4-receptor (MC4R) deficiency, but also leptin receptor (LEPR), pro-opiomelanocortin (POMC), and secondary hypothalamic injury, most commonly craniopharyngiomas. Most childhood obesity, however, is polygenic, arising from interactions of environmental and genetic factors. In many patients, no clear etiology is identified. Treatment remains challenging, particularly if hyperphagia and reduced satiety are predominant presenting features. We describe the case of a 19-year-old male with a history of autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), type 2 diabetes mellitus (T2DM) and morbid obesity, who showed a clinically significant response to tirzepatide therapy following failed conventional interventions. This case highlights the potential role of dual incretin therapy in adolescents with severe early-onset obesity and hyperphagia, even in the absence (based on present knowledge) of identifiable hypothalamic or genetic pathology. Show less

Thyroid carcinoma is the most prevalent endocrine cancer globally and the primary cause of cancer-related mortality. Epigenetic modifications are progressively being linked to metastasis. This study aimed to examine whole-genome DNA methylation patterns and the gene expression profiles in thyroid cancer tissue samples using a MethylationEPIC BeadChip (850K), RNA sequencing, and a targeted bisulfite sequencing assay. The results of the Illumina Infinium human methylation kit (850K) analyses identified differentially methylated CpG locations (DMPs) and differentially methylated CpG regions (DMRs) encompassing nearly the entire genome with high resolution and depth. Gene ontology and KEGG pathway analyses revealed that the genes associated with DMRs belonged to various domain-specific ontologies, including cell adhesion, molecule binding, and proliferation. The RNA-Seq study found 1627 differentially expressed genes, 1174 of which that were up-regulated and 453 of which that were down-regulated. The targeted bisulfite sequencing assay revealed that CHST2, DPP4, DUSP6, ITGA2, SLC1A5, TIAM1, TNIK, and ABTB2 methylation levels were dramatically lowered in thyroid cancer patients when compared to the controls, but GALNTL6, HTR7, SPOCD1, and GRM5 methylation levels were significantly raised. Our study revealed that the whole-genome DNA methylation patterns and gene expression profiles in thyroid cancer shed new light on the tumorigenesis of thyroid cancer. Show less