We found a sporadic case of mental retardation, associated to short stature and constipation. We investigated the possible genetic origin of the syndrome. Clinical and biochemical investigations were conducted. Exome sequencing was used to search for pathogenic variations. A de novo mutation (c.1183G>T, p.E395X) was found in one allele of the THRA gene. The mutation creates a stop codon, which eliminates the C-terminal helix of the TRα1 receptor for thyroid hormone. The patient presents typical symptoms for the RTHα genetic disease, but has a normal head circumference. There are now 21 known mutations in THRA. All mutations which alter the C-terminal helix of TRα1 lead to severe forms of RTHα.

High-fat intake and subsequent obesity are associated with premature onset of puberty, but the exact neuroendocrine mechanisms are still unclear. The transcriptional factor p53 has been predicted to be a central hub of the gene networks controlling the pubertal onset. Besides, p53 also plays crucial roles in metabolism. Here, we explored p53 in the hypothalami of mice fed a high-fat diet (HFD), which showed an up-regulated expression. Besides, we also revealed that overexpressed p53 may accelerate hypothalamo-pituitary-gonadal (HPG) axis activation partially through the c-Myc/Lin28/let-7 system. These results can deepen our understanding of the interaction between metabolic regulation and puberty onset control, and may shed light on the neuroendocrine mechanisms of obesity-related central precocious puberty.

Purpose: CTRP3 is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The current study aimed to investigate the potential role of CTRP3 in obese children and explore its relationships with insulin sensitivity, pancreatic β cell function, and obesity-related markers. Patients and methods: We studied the levels of serum CTRP3 in 48 obese and 36 normal weight pre-puberty children. The levels of blood pressure, lipids, glucose, and insulin were measured, and the values of HOMA-IR, HOMA-β and insulinogenic index were calculated. The correlations of these measurements with CTRP3 levels were analyzed. Results: In this study, we found that CTRP3 serum levels significantly decreased in obese children compared to controls, and insulin resistant obese subjects have lower CTRP3 levels in contrast with the non-insulin resistant obese subjects. Moreover, serum CTRP3 concentrations significantly decreased, while glucose and insulin concentrations significantly increased after a 3 hrs oral glucose tolerance test in obese children. Furthermore, Serum CTRP3 levels correlated negatively and significantly with BMI, triglycerides, systolic blood pressure, fasting insulin, glucose, HOMA-IR, HOMA-β and insulinogenic index in obese children. Conclusion: In summary, serum CTRP3 levels significantly decreased in obese children, and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, CTRP3 may play a protective role in the glucose homeostasis and tightly related to β cell function as well as obesity-related markers in obese children.

BACKGROUND:The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. MATERIAL AND METHODS:Myocardial ischemia-reperfusion in wild-type...

Background. Central precocious puberty (CPP) is defined by gonadotropin-dependent development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. MKRN3 and DLK1 are two genes, disease-causing variants of which have recently been discovered to cause idiopathic CPP. Methods. We screened 173 Chinese patients (9 males and 164 females; 9 familial and 164 sporadic) with ICPP and 43 patients (9 males and 34 females; 3 familial and 40 sporadic) with early puberty for variants in MKRN3. We also screened 19 patients with ICPP and early puberty for variants of DLK1 (17 males and 2 females; 5 familial and 14 sporadic). Results. We identified four novel missense variants of MKRN3, c.1138G > A (p.Glu380Lys), c.1420T > A (p.Leu474Met), c.673C > G (p.Leu225Val), and c.1071C > G (p.Ile357Met) in two sporadic cases and three familial cases. According to ACMG standards, two MKRN3 variant (p.Glu380Lys and p.Ile357Met) are likely pathogenic, and two others are of uncertain significance. We also performed bioinformatic analysis to evaluate the impact of variants on MKRN3 protein structures, which showed that Ile357Met locates at the zinc-binding region (C3HC4 RING finger motif), while Glu380Lys is spatially extremely close to the C3HC4 RING finger, MKRN-specific Cys-His domain, and the third C3H1 zinc-finger motif region. Per Glu380Lys, Glu with negative charges has been changed into Lys with positive charges, which may affect the hydrogen bond formation between amino acids and the stability of the local structure, thus affecting the binding of zinc iron to MKRN3 protein. Besides, we did not identify any variants of DLK1 gene in our patients. Conclusions. In this study, we report four novel MKRN3 variants in patients with ICPP. Moreover, we did not find any variants of DLK1 gene. Variants of MKRN3 are relatively uncommon in Chinese ICPP patients.